bluuebunny/crossref_metadata_2025 huggingface dataset:
Temozolomide Treatment Induces HMGB1 to Promote the Formation of Glioma Stem Cells via the TLR2/NEAT1/Wnt Pathway in Glioblastoma
Authors: Gao Xiang-Yu , Zang Jian , Zheng Min-Hua , Zhang Yu-Fei , Yue Kang-Yi , Cao Xiu-Li , Cao Yuan , Li Xin-Xin , Han Hua , Jiang Xiao-Fan , Liang Liang
Published: February 2021

Formation of glioma stem cells (GSCs) is considered as one of the main reasons of temozolomide (TMZ) resistance in glioma patients. Recent studies have shown that tumor microenvironment-derived signals could promote GSCs formation. But the critical molecule and underlying mechanism for GSCs formation after TMZ treatment is not entirely identified. Our study showed that TMZ treatment promoted GSCs formation by glioma cells; TMZ treatment of biopsy-derived glioblastoma multiforme cells upregulated HMGB1; HMGB1 altered gene expression profile of glioma cells with respect to mRNA, lncRNA and miRNA. Furthermore, our results showed that TMZ-induced HMGB1 increased the formation of GSCs and when HMGB1 was downregulated, TMZ-mediated GSCs formation was attenuated. Finally, we showed that the effect of HMGB1 on glioma cells was mediated by TLR2, which activated Wnt/β-catenin signaling to promote GSCs. Mechanistically, we found that HMGB1 upregulated NEAT1, which was responsible for Wnt/β-catenin activation. In conclusion, TMZ treatment upregulates HMGB1, which promotes the formation of GSCs via the TLR2/NEAT1/Wnt pathway. Blocking HMGB1-mediated GSCs formation could serve as a potential therapeutic target for preventing TMZ resistance in GBM patients.
Induced Arp2/3 Complex Depletion Increases FMNL2/3 Formin Expression and Filopodia Formation
Authors: Dimchev Vanessa , Lahmann Ines , Koestler Stefan A. , Kage Frieda , Dimchev Georgi , Steffen Anika , Stradal Theresia E. B. , Vauti Franz , Arnold Hans-Henning , Rottner Klemens
Published: February 2021

The Arp2/3 complex generates branched actin filament networks operating in cell edge protrusion and vesicle trafficking. Here we employ a conditional knockout mouse model permitting tissue- or cell-type specific deletion of the murine Actr3 gene (encoding Arp3). A functional Actr3 gene appeared essential for fibroblast viability and growth. Thus, we developed cell lines for exploring the consequences of acute, tamoxifen-induced Actr3 deletion causing near-complete loss of functional Arp2/3 complex expression as well as abolished lamellipodia formation and membrane ruffling, as expected. Interestingly, Arp3-depleted cells displayed enhanced rather than reduced cell spreading, employing numerous filopodia, and showed little defects in the rates of random cell migration. However, both exploration of new space by individual cells and collective migration were clearly compromised by the incapability to efficiently maintain directionality of migration, while the principal ability to chemotax was only moderately affected. Examination of actin remodeling at the cell periphery revealed reduced actin turnover rates in Arp2/3-deficient cells, clearly deviating from previous sequestration approaches. Most surprisingly, induced removal of Arp2/3 complexes reproducibly increased FMNL formin expression, which correlated with the explosive induction of filopodia formation. Our results thus highlight both direct and indirect effects of acute Arp2/3 complex removal on actin cytoskeleton regulation.
Hydrogen Oxidation Pathway Over Ni–Ceria Electrode: Combined Study of DFT and Experiment
Authors: Jiang Yunan , Wang Shuang , Xu Jun , Zheng Minghao , Yang Yi , Wu Xiaojun , Xia Changrong
Published: February 2021

Ni–ceria cermets are potential anodes for intermediate-temperature solid oxide fuel cells, thanks to the catalytic activity and mixed conductivities of ceria-based materials associated with the variable valence states of cerium. However, the anodic reaction mechanism in the Ni–ceria systems needs to be further revealed. Via density functional theory with strong correlated correction method, this work gains insight into reaction pathways of hydrogen oxidation on a model system of Ni10-CeO2(111). The calculation shows that electrons tend to be transferred from Ni10 cluster to cerium surface, creating surface oxygen vacancies. Six pathways are proposed considering different adsorption sites, and the interface pathway proceeding with hydrogen spillover is found to be the prevailing process, which includes a high adsorption energy of −1.859 eV and an energy barrier of 0.885 eV. The density functional theory (DFT) calculation results are verified through experimental measurements including electrical conductivity relaxation and temperature programmed desorption. The contribution of interface reaction to the total hydrogen oxidation reaction reaches up to 98%, and the formation of Ni–ceria interface by infiltrating Ni to porous ceria improves the electrochemical activity by 72% at 800°C.
A Novel Cr2O3/MnO2-x Electrode for Lithium-Oxygen Batteries with Low Charge Voltage and High Energy Efficiency
Authors: Wei Zhaohuan , Zhang Zhiyuan , Ren Yaqi , Zhao Hong
Published: February 2021

A high energy efficiency, low charging voltage cathode is of great significance for the development of non-aqueous lithium-oxygen batteries. Non-stoichiometric manganese dioxide (MnO2-x) and chromium trioxide (Cr2O3) are known to have good catalytic activities for the discharging and charging processes, respectively. In this work, we prepared a cathode based on Cr2O3 decorated MnO2-x nanosheets via a simple anodic electrodeposition-electrostatic adsorption-calcination process. This combined fabrication process allowed the simultaneous introduction of abundant oxygen vacancies and trivalent manganese into the MnO2-x nanosheets, with a uniform load of a small amount of Cr2O3 on the surface of the MnO2-x nanosheets. Therefore, the Cr2O3/MnO2-x electrode exhibited a high catalytic effect for both discharging and charging, while providing high energy efficiency and low charge voltage. Experimental results show that the as-prepared Cr2O3/MnO2-x cathode could provide a specific capacity of 6,779 mA·h·g−1 with a terminal charge voltage of 3.84 V, and energy efficiency of 78%, at a current density of 200 mA·g−1. The Cr2O3/MnO2-x electrode also showed good rate capability and cycle stability. All the results suggest that the as-prepared Cr2O3/MnO2-x nanosheet electrode has great prospects in non-aqueous lithium-oxygen batteries.
Role of the Orphan Nuclear Receptor NR4A Family in T-Cell Biology
Authors: Odagiu Livia , May Julia , Boulet Salix , Baldwin Troy A. , Labrecque Nathalie
Published: February 2021

The nuclear orphan receptors NR4A1, NR4A2, and NR4A3 are immediate early genes that are induced by various signals. They act as transcription factors and their activity is not regulated by ligand binding and are thus regulated via their expression levels. Their expression is transiently induced in T cells by triggering of the T cell receptor following antigen recognition during both thymic differentiation and peripheral T cell responses. In this review, we will discuss how NR4A family members impact different aspects of the life of a T cell from thymic differentiation to peripheral response against infections and cancer.
Coupling Coordination and Spatiotemporal Dynamic Evolution Between Green Urbanization and Green Finance: A Case Study in China
Authors: Dong Guanglong , Ge Yibing , Zhu Weiya , Qu Yanbo , Zhang Wenxin
Published: February 2021

This study constructed a comprehensive index system and employed a coupling coordination degree model, global spatial autocorrelation models, and local spatial autocorrelation models to quantitatively investigate the spatiotemporal characteristics and dynamic mechanism of the coupling coordination relationship between green urbanization and green finance in China during 2010–2017. The results showed that the level of green urbanization and green finance improved over the study period, but the development of green finance lagged behind the pace of green urbanization and the comprehensive score was still low. The coupling coordination degree presented a trend of continuous optimization, with coordination in eastern China being clearly higher than in central, western, and northeastern China. Furthermore, there was both spatial dependency and spatial heterogeneity in the coupling coordination degree between green urbanization and green finance. Provinces with a high-high clustering mode were mainly distributed in the eastern region, while provinces in western and northeastern China mainly had a low-low clustering mode in 2010. The high-high clustering mode gradually expanded from eastern to central China, while most provinces in western and northeastern China still exhibited low-low clustering in 2017. This indicates that the coupling coordination degree between green urbanization and green finance had strong spatial agglomeration and spatial spillover effects in central and eastern China, while in western and northeastern China its development was still poor.
Vegetation Restoration Alters Fungal Community Composition and Functional Groups in a Desert Ecosystem
Authors: Zhang Ying , Cao Hongyu , Zhao Peishan , Wei Xiaoshuai , Ding Guodong , Gao Guanglei , Shi Mingchang
Published: February 2021

Revegetation is regarded as an effective means to improve the ecological environment in deserts and profoundly influences the potential ecological functions of the soil fungal community. Therefore, Illumina high-throughput sequencing was performed to characterize the soil fungal diversity and community composition at two soil depths (0–10 cm and 10–20 cm) with four revegetation durations (natural grassland, half-mature, nearly mature, and mature Pinus. sylvestris var. mongolica plantations) in the Mu Us Sandy Land, China. The effects of soil properties on soil fungal communities were also examined to reveal the connection between fungal function and soil environment. The results indicated that 1) soil nutrient content and enzyme activity showed significant differences through the restoration durations, 2) there was no significant effect of soil depth on soil fungal diversity, while the Shannon diversity index of all fungal communities was significantly different among different revegetation durations, 3) compared with grassland, ectomycorrhizal fungi (notably, Inocybe, Tuber, and Calostoma) were abundant in plantations. The endophyte fungus Mortierella was among the top 10 genera in all soil samples and arbuscular mycorrhizal fungus Diversispora was the indicator genus of the grassland, and 4) catalase and total nitrogen were the main factors affecting fungal community composition and were closely related to saprotrophs and pathotrophs, respectively. This new information indicates the variation of soil fungal communities along revegetation durations and highlights the interaction between fungal functions and desert ecosystems.
CDK6 Is a Potential Prognostic Biomarker in Acute Myeloid Leukemia
Authors: Liu Wei , Yi Jin-Mou , Liu Yi , Chen Cong , Zhang Kai-Xuan , Zhou Cheng , Zhan Hui-En , Zhao Liang , Morales Stephanie , Zhao Xie-Lan , Zeng Hui
Published: February 2021

Acute myeloid leukemia (AML) is a threatening hematological malignant disease in which new successful approaches in therapy are needed. Cyclin-dependent kinase 6 (CDK6), a regulatory enzyme of the cell cycle that plays an important role in leukemogenesis and the maintenance of leukemia stem cells (LSC), has the potential to predict the prognosis of AML. By analyzing public databases, we observed that the messenger RNA (mRNA) levels of CDK6 were significantly overexpressed in AML cell lines and non-acute promyelocytic leukemia (non-APL) AML patients when compared to healthy donors. Furthermore, CDK6 expression was significantly reduced in AML patients who achieved complete remission (CR) compared to that at the time of diagnosis in our validated cohort. The expression of CDK6 was tightly correlated with peripheral blood blasts, French–American–British (FAB) subtypes, CCAAT-enhancer-binding protein α (CEBPA) mutation, and chromosomal abnormalities of t(8;21). However, the clinical significance and effects of CDK6 expression on the prognosis of non-APL AML patients remain uncertain. We found that CDK6 expression was inversely correlated with overall survival (OS) among non-APL AML patients using the Kaplan–Meier analysis. CDK6 was also found to be positively associated with genes identified to contribute to the development of leukemia, including CCND2, DNMT3B, SOX4, and IKZF2, as well as being negatively associated with anticancer microRNAs, including miR-187, miR-9, miR-582, miR708, and miR-362. In summary, our study revealed that CDK6 might be a potential diagnostic and prognostic biomarker in non-APL AML patients.
The Important Role of Leptin in Modulating the Risk of Dermatological Diseases
Authors: Su Xin , Cheng Ye , Chang Dong
Published: February 2021

It is an indisputable fact that obesity is associated with a series of health problems. One important hallmark of obesity is excessive accumulation of lipids in the adipocyte, especially triglyceride (TG). Currently, the adipocyte has been considered not only as a huge repository of excess energy in the form of fat but also as an important source of multiple hormones and cytokines called adipokines. In obesity, the adipocyte is dysfunctional with excessive production and secretion of pro-inflammatory adipokines, such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and leptin. On the other hand, accumulating evidence has shown that leptin plays a vital role in stimulating angiogenesis, controlling lipid metabolism, and modulating the production of pro-inflammatory cytokines. Furthermore, the various activities of leptin are related to the wide distribution of leptin receptors. Notably, it has been reported that enhanced leptin levels and dysfunction of the leptin signaling pathway can influence diverse skin diseases. Recently, several studies revealed the roles of leptin in wound healing, the hair cycle, and the pathogenic development of skin diseases, such as psoriasis, lupus erythematosus, and dermatological cancers. However, the exact mechanisms of leptin in modulating the dermatological diseases are still under investigation. Therefore, in the present review, we summarized the regulatory roles of leptin in the pathological progression of diverse diseases of skin and skin appendages. Furthermore, we also provided evidence to elucidate the complicated relationship between leptin and different dermatological diseases, such as systemic lupus erythematosus (SLE), psoriasis, hidradenitis suppurativa, and some skin tumors.
Transcriptomic Analysis of Rat Macrophages
Authors: Pridans Clare , Irvine Katharine M. , Davis Gemma M. , Lefevre Lucas , Bush Stephen J. , Hume David A.
Published: February 2021

The laboratory rat is widely used as a model for human diseases. Many of these diseases involve monocytes and tissue macrophages in different states of activation. Whilst methods forin vitrodifferentiation of mouse macrophages from embryonic stem cells (ESC) and bone marrow (BM) are well established, these are lacking for the rat. The gene expression profiles of rat macrophages have also not been characterised to the same extent as mouse. We have established the methodology for production of rat ESC-derived macrophages and compared their gene expression profiles to macrophages obtained from the lung and peritoneal cavity and those differentiated from BM and blood monocytes. We determined the gene signature of Kupffer cells in the liver using rats deficient in macrophage colony stimulating factor receptor (CSF1R). We also examined the response of BM-derived macrophages to lipopolysaccharide (LPS). The results indicate that many, but not all, tissue-specific adaptations observed in mice are conserved in the rat. Importantly, we show that unlike mice, rat macrophages express the CSF1R ligand, colony stimulating factor 1 (CSF1).
CD8+CD161+ T-Cells: Cytotoxic Memory Cells With High Therapeutic Potential
Authors: Konduri Vanaja , Oyewole-Said Damilola , Vazquez-Perez Jonathan , Weldon Scott A. , Halpert Matthew M. , Levitt Jonathan M. , Decker William K.
Published: February 2021

NK1.1 and its human homolog CD161 are expressed on NK cells, subsets of CD4+and CD8+T cells, and NKT cells. While the expression of NK1.1 is thought to be inhibitory to NK cell function, it is reported to play both costimulatory and coinhibitory roles in T-cells. CD161 has been extensively studied and characterized on subsets of T-cells that are MR1-restricted, IL-17 producing CD4+(TH17 MAIT cells) and CD8+T cells (Tc17 cells). Non-MAIT, MR1-independent CD161-expressing T-cells also exist and are characterized as generally effector memory cells with a stem cell like phenotype. Gene expression analysis of this enigmatic subset indicates a significant enhancement in the expression of cytotoxic granzyme molecules and innate like stress receptors in CD8+NK1.1+/CD8+CD161+cells in comparison to CD8+cells that do not express NK1.1 or CD161. First identified and studied in the context of viral infection, the role of CD8+CD161+T-cells, especially in the context of tumor immunology, is still poorly understood. In this review, the functional characteristics of the CD161-expressing CD8+T cell subset with respect to gene expression profile, cytotoxicity, and tissue homing properties are discussed, and application of this subset to immune responses against infectious disease and cancer is considered.
Interleukin-33 Amplifies Human Mast Cell Activities Induced by Complement Anaphylatoxins
Authors: West Peter W. , Bahri Rajia , Garcia-Rodriguez Karen M. , Sweetland Georgia , Wileman Georgia , Shah Rajesh , Montero Angeles , Rapley Laura , Bulfone-Paus Silvia
Published: February 2021

Both, aberrant mast cell responses and complement activation contribute to allergic diseases. Since mast cells are highly responsive to C3a and C5a, while Interleukin-33 (IL-33) is a potent mast cell activator, we hypothesized that IL-33 critically regulates mast cell responses to complement anaphylatoxins. We sought to understand whether C3a and C5a differentially activate primary human mast cells, and probe whether IL-33 regulates C3a/C5a-induced mast cell activities. Primary human mast cells were generated from peripheral blood precursors or isolated from healthy human lung tissue, and mast cell complement receptor expression, degranulation, mediator release, phosphorylation patterns, and calcium flux were assessed. Human mast cells of distinct origin express constitutively higher levels of C3aR1 than C5aR1, and both receptors are downregulated by anaphylatoxins. While C3a is a potent mast cell degranulation inducer, C5a is a weaker secretagogue with more delayed effects. Importantly, IL-33 potently enhances the human mast cell reactivity to C3a and C5a (degranulation, cytokine and chemokine release), independent of changes in C3a or C5a receptor expression or the level of Ca2+influx. Instead, this reflects differential dynamics of intracellular signaling such as ERK1/2 phosphorylation. Since primary human mast cells respond differentially to anaphylatoxin stimulation, and that IL-33 is a key regulator of mast cell responses to complement anaphylatoxins, this is likely to aggravate Th2 immune responses. This newly identified cross-regulation may be important for controlling exacerbated complement- and mast cell-dependent Th2 responses and thus provides an additional rationale for targeting anti-IL33 therapeutically in allergic diseases.
Current Insights and Future Prospects for Targeting IL-17 to Treat Patients With Systemic Lupus Erythematosus
Authors: Koga Tomohiro , Ichinose Kunihiro , Kawakami Atsushi , Tsokos George C.
Published: February 2021

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune cell abnormalities which lead to the production of autoantibodies and the deposition of immune complexes. Interleukin (IL)-17-producing cells play an important role in the pathogenesis of the disease, making them an attractive therapeutic target. Studies in lupus-prone mice and ofex vivocells from patients with SLE humans have shown that IL-17 represents a promising therapeutic target. Here we review molecular mechanisms involved in IL-17 production and Th17 cell differentiation and function and an update on the role of IL-17 in autoimmune diseases and the expected usefulness for targeting IL-17 therapeutically.
Successful HCV Therapy Reduces Liver Disease Severity and Inflammation Biomarkers in HIV/HCV-Coinfected Patients With Advanced Cirrhosis: A Cohort Study
Authors: Medrano Luz Maria , Berenguer Juan , Salgüero Sergio , González-García Juan , Díez Cristina , Hontañón Víctor , Garcia-Broncano Pilar , Ibañez-Samaniego Luis , Bellón José M. , Jiménez-Sousa María Angeles , Resino Salvador
Published: February 2021

Background: Eradication of hepatitis C virus (HCV) promotes an improvement in liver disease and the deactivation of the immune system. Here, we aimed to evaluate the changes in liver disease scores and plasma biomarkers following HCV clearance with direct-acting antivirals (DAAs) in HIV-infected patients with advanced HCV-related cirrhosis.

Methods: We performed an observational study of 50 patients with advanced cirrhosis who received DAAs therapy. Variables were assessed at baseline and 48 weeks after HCV treatment completion. Epidemiological and clinical data were collected through an online form. Liver stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and Child-Pugh-Turcotte (CTP) were evaluated by physicians. Plasma biomarkers were measured by multiplex immunoassay.

Results: We found significant decreases in severity scores of liver disease [LSM (q-value < 0.001), HVPG (q-value = 0.011), and CTP (q-value = 0.045)] and plasma biomarkers [LBP (q-value < 0.001), IP-10 (q-value < 0.001), IL-8 (q-value < 0.001), IL-18 (q-value < 0.001), IL-1RA (q-value = 0.013), OPG (q-value < 0.001), sVCAM-1 (q-value < 0.001), sICAM-1 (q-value < 0.001), PAI-1 (q-value = 0.001), and VEGF-A (q-value = 0.006)]. We also found a significant direct association between the change in LSM values and the change in values of LBP (q-value < 0.001), IP-10 (q-value < 0.001), MCP-1 (q-value = 0.008), IL-8 (q-value < 0.001), IL-18 (q-value < 0.001), OPG (q-value = 0.004), sVCAM-1 (q-value < 0.001), sICAM-1 (q-value < 0.001), and PAI-1 (q-value = 0.002). For CTP values, we found significant positive associations with IP-10 (q-value = 0.010), IL-6 (q-value = 0.010), IL-1RA (q-value = 0.033), and sICAM-1 (q-value = 0.010).

Conclusion: The HCV eradication with all-oral DAAs in HIV/HCV-coinfected patients with advanced cirrhosis promoted an improvement in the severity of advanced cirrhosis and plasma biomarkers (inflammation, coagulopathy, and angiogenesis). The decrease in plasma biomarkers was mainly related to the reduction in LSM values.
Comprehensive Succinylome Profiling Reveals the Pivotal Role of Lysine Succinylation in Energy Metabolism and Quorum Sensing of Staphylococcus epidermidis
Authors: Zhao Yiping , Han Yang , Sun Yuzhe , Wei Zhendong , Chen Jialong , Niu Xueli , An Qian , Zhang Li , Qi Ruiqun , Gao Xinghua
Published: February 2021

Background

Lysine succinylation is a newly identified posttranslational modification (PTM), which exists widely from prokaryotes to eukaryotes and participates in various cellular processes, especially in the metabolic processes. Staphylococcus epidermidis is a commensal bacterium in the skin, which attracts more attention as a pathogen, especially in immunocompromised patients and neonates by attaching to medical devices and forming biofilms. However, the significance of lysine succinylation in S. epidermidis proteins has not been investigated.

Objectives

The purpose of this study was to investigate the physiological and pathological processes of S. epidermidis at the level of PTM. Moreover, by analyzing previous succinylome datasets in various organisms, we tried to provide an in-depth understanding of lysine succinylation.

Methods

Using antibody affinity enrichment followed by LC-MS/MS analysis, we examined the succinylome of S. epidermidis (ATCC 12228). Then, bioinformatics analysis was performed, including Gene Ontology (GO), KEGG enrichment, motif characterization, secondary structure, protein–protein interaction, and BLAST analysis.

Results

A total of 1557 succinylated lysine sites in 649 proteins were identified in S. epidermidis (ATCC 12228). Among these succinylation proteins, GO annotation showed that proteins related to metabolic processes accounted for the most. KEGG pathway characterization indicated that proteins associated with the glycolysis/gluconeogenesis and citrate cycle (TCA cycle) pathway were more likely to be succinylated. Moreover, 13 conserved motifs were identified. The specific motif KsuD was conserved in model prokaryotes and eukaryotes. Succinylated proteins with this motif were highly enriched in the glycolysis/gluconeogenesis pathway. One succinylation site (K144) was identified in S-ribosylhomocysteine lyase, a key enzyme in the quorum sensing system, indicating the regulatory role succinylation may play in bacterial processes. Furthermore, 15 succinyltransferases and 18 desuccinylases (erasers) were predicted in S. epidermidis by BLAST analysis.

Conclusion

We performed the first comprehensive profile of succinylation in S. epidermidis and illustrated the significant role succinylation may play in energy metabolism, QS system, and other bacterial behaviors. This study may be a fundamental basis to investigate the underlying mechanisms of colonization, virulence, and infection of S. epidermidis, as well as provide a new insight into regulatory effects succinylation may lay on metabolic processes (Data are available via ProteomeXchange with identifier PXD022866).
Reductive Transformation of Fe(III) (oxyhydr)Oxides by Mesophilic Homoacetogens in the Genus Sporomusa
Authors: Igarashi Kensuke , Kato Souichiro
Published: February 2021

Microbial reduction of iron contributes to the dissolution and transformation of iron-containing minerals in nature. Diverse groups of homoacetogenic bacteria (homoacetogens) have been reported to reduce insoluble Fe(III) oxides, such as hydrous ferric oxide (HFO), an Fe(III) mineral commonly found in soils and sediments. Several members of genus Sporomusa reportedly oxidize Fe(0), indicating the presence of an extracellular electron-uptake mechanism. However, the ability of the genus to reduce insoluble Fe(III) oxides is limited, and the underlying reduction mechanism remains to be elucidated. In this study, the HFO reduction ability of three Sporomusa spp. (Sporomusa sp. strain GT1, Sporomusa sphaeroides, and Sporomusa ovata) and a homoacetogen of a different genus (Acetobacterium woodii) were assayed under organotrophic (ethanol) and lithotrophic (H2 + CO2) conditions without a chelator or reducing reagent. All tested homoacetogens showed acetogenic growth and concomitant reduction of HFO under both organotrophic and lithotrophic conditions. Analysis of the growth stoichiometry showed that Fe(III) reduction does not support direct energy conservation, thereby indicating that Fe(III) reduction is a side reaction of acetogenesis to dissipate the excess reducing power. HFO was reduced to a soluble Fe(II) form by microbial activity. In addition, we observed that strain GT1, S. sphaeroides, and S. ovata reduced crystalline Fe(III) oxides, and HFO was reductively transformed into magnetite (Fe3O4) under phosphate-limiting conditions. Separation of HFO by a dialysis membrane still permitted Fe(II) production, although the reduction rate was decreased, suggesting that Fe(III) reduction is at least partially mediated by soluble redox compound(s) secreted from the cells. Finally, culture experiments and comparative genomic analysis suggested that electron transfer by flavins and multiheme c-type cytochrome were not directly correlated with Fe(III) reduction activity. This study reveals the capability of Sporomusa spp. in the reductive transformation of iron mineral and indicates the potential involvement of these organisms in iron and other mineral cycles in nature.
Soil Disturbance Affects Plant Productivity via Soil Microbial Community Shifts
Authors: Seitz Taylor J. , Schütte Ursel M. E. , Drown Devin M.
Published: February 2021

Recent advances in climate research have discovered that permafrost is particularly vulnerable to the changes occurring in the atmosphere and climate, especially in Alaska where 85% of the land is underlain by mostly discontinuous permafrost. As permafrost thaws, research has shown that natural and anthropogenic soil disturbance causes microbial communities to undergo shifts in membership composition and biomass, as well as in functional diversity. Boreal forests are home to many plants that are integral to the subsistence diets of many Alaska Native communities. Yet, it is unclear how the observed shifts in soil microbes can affect above ground plant communities that are relied on as a major source of food. In this study, we tested the hypothesis that microbial communities associated with permafrost thaw affect plant productivity by growing five plant species found in Boreal forests and Tundra ecosystems, including low-bush cranberry and bog blueberry, with microbial communities from the active layer soils of a permafrost thaw gradient. We found that plant productivity was significantly affected by the microbial soil inoculants. Plants inoculated with communities from above thawing permafrost showed decreased productivity compared to plants inoculated with microbes from undisturbed soils. We used metagenomic sequencing to determine that microbial communities from disturbed soils above thawing permafrost differ in taxonomy from microbial communities in undisturbed soils above intact permafrost. The combination of these results indicates that a decrease in plant productivity can be linked to soil disturbance driven changes in microbial community membership and abundance. These data contribute to an understanding of how microbial communities can be affected by soil disturbance and climate change, and how those community shifts can further influence plant productivity in Boreal forests and more broadly, ecosystem health.
Systemic Inflammation Increases the Susceptibility to Levodopa-Induced Dyskinesia in 6-OHDA Lesioned Rats by Targeting the NR2B-Medicated PKC/MEK/ERK Pathway
Authors: Yan Aijuan , Song Lu , Zhang Yu , Wang Xijin , Liu Zhenguo
Published: February 2021

Background: The long-term administration of levodopa (L-dopa), the gold-standard treatment for Parkinson's disease (PD), is irreparably associated with L-dopa-induced dyskinesia (LID), which dramatically affects the quality of life of patients. However, the underlying molecular mechanisms of how LID exacerbates remain unknown. Neuroinflammation in the striatum plays an active role in LID. These findings prompt an investigation of non-neuronal mechanisms of LID. This study will examine the effects of systemic inflammation in the development and progression of LID.

Methods: To evaluate the possible influence of systemic inflammation in the appearance of LID, the PD rats received an intraperitoneal (IP) injection of various concentrations of lipopolysaccharides (LPS, 1, 2, and 5 mg/kg) or saline. One day later, these PD rats started to receive daily treatment with L-dopa (6 mg/kg) along with benserazide (6 mg/kg) or saline for 21 days, and dyskinesia was evaluated at several time points. Moreover, the activation of microglia and astrocytes and the molecular changes in NR2B and mGLUR5 signaling pathways were measured.

Results: We found that systemic inflammatory stimulation with LPS exacerbated the intensity of abnormal involuntary movements (AIMs) induced by L-dopa treatment in 6-hydroxydopamine (6-OHDA) lesioned rats. The LPS injection activated the gliocytes and increased the levels of proinflammatory cytokines in the striatum in LID rats. The PD rats that received the LPS injection showed the overexpression of p-NR2B and NR2B, as well as activated PKC/MEK/ERK and NF-κB signal pathways in response to the L-dopa administration. On the contrary, clodronate-encapsulated liposomes (Clo-lipo), which could suppress the inflammatory response induced by peripheral LPS injection, improved behavioral dysfunction, inhibited neuroinflammation, prevented NR2B overexpression, and decreased the phosphorylation of PKC/MEK/ERK and NF-κB signaling pathways.

Conclusion: This study suggests that systemic inflammation, by exacerbating preexisting neuroinflammation and facilitating NR2B subunit activity, may play a crucial role in the development of LID. The administration of Clo-lipo restores the effects of LPS and decreases the susceptibility to LID in 6-OHDA lesioned rats.
Reduced Facilitation of Parietal-Motor Functional Connections in Older Adults
Authors: Goldenkoff Elana R. , Logue Rachel N. , Brown Susan H. , Vesia Michael
Published: February 2021

Age-related changes in cortico-cortical connectivity in the human motor network in older adults are associated with declines in hand dexterity. Posterior parietal cortex (PPC) is strongly interconnected with motor areas and plays a critical role in many aspects of motor planning. Functional connectivity measures derived from dual-site transcranial magnetic stimulation (dsTMS) studies have found facilitatory inputs from PPC to ipsilateral primary motor cortex (M1) in younger adults. In this study, we investigated whether facilitatory inputs from PPC to M1 are altered by age. We used dsTMS in a conditioning-test paradigm to characterize patterns of functional connectivity between the left PPC and ipsilateral M1 and a standard pegboard test to assess skilled hand motor function in 13 young and 13 older adults. We found a PPC-M1 facilitation in young adults but not older adults. Older adults also showed a decline in motor performance compared to young adults. We conclude that the reduced PPC-M1 facilitation in older adults may be an early marker of age-related decline in the neural control of movement.
Label-Free Liquid Chromatography–Mass Spectrometry Proteomic Analysis of Urinary Identification in Diabetic Vascular Dementia in a Han Chinese Population
Authors: Chen Ruijuan , Yi Yuanjing , Xiao Wenbiao , Zhong Bowen , Shu Yi , Zhang Le , Zeng Yi
Published: February 2021

Objective:This study aimed to identify potential diagnostic biomarkers of diabetic vascular dementia (DVD) and unravel the underlying mechanisms using mass spectrometry (MS).

Methods:Label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis was applied to urine samples from four groups, including 14 patients with vascular dementia (VD), 22 patients with type 2 diabetes mellitus (T2DM), 12 patients with DVD, and 21 normal controls (NCs). Searching the MS data by Proteome Discoverer software (ThermoFisher Scientific; Waltham, MA, USA), protein abundances were analyzed qualitatively and quantitatively and compared between these groups. Combining bioinformatics analysis using Gene Ontology (GO), pathway crosstalk analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI) network analysis using STRING, and literature searching, the differentially expressed proteins (DEPs) of DVD can be comprehensively judged and were further quantified by receiver operating characteristic (ROC) curve methods.

Results:The proteomic findings showed quantitative changes in patients with DVD compared to patients with NC, T2DM, and VD groups; among 4,744 identified urine proteins, 1,222, 1,152, and 1,180 proteins displayed quantitative changes unique to DVD vs. NC, T2DM, and VD, respectively, including 481 overlapped common DEPs. Then, nine unique proteins [including HP, SERPIND, ATP5PB, VNN2, ALDH3A1, U2AF2, C6, A0A5C2GRG5 (no name), and A0A5C2FZ29 (no name)] and two composite markers (CM) (A0A5C2GRG5+U2AF2 and U2AF2+C6) were confirmed by a ROC curve method.

Conclusion:This study provided an insight into the potential pathogenesis of DVD and elucidated a method for early detection.
Naturalistic Intensities of Light at Night: A Review of the Potent Effects of Very Dim Light on Circadian Responses and Considerations for Translational Research
Authors: Walbeek Thijs J. , Harrison Elizabeth M. , Gorman Michael R. , Glickman Gena L.
Published: February 2021

In this review, we discuss the remarkable potency and potential applications of a form of light that is often overlooked in a circadian context: naturalistic levels of dim light at night (nLAN), equivalent to intensities produced by the moon and stars. It is often assumed that such low levels of light do not produce circadian responses typically associated with brighter light levels. A solid understanding of the impacts of very low light levels is complicated further by the broad use of the somewhat ambiguous term “dim light,” which has been used to describe light levels ranging seven orders of magnitude. Here, we lay out the argument that nLAN exerts potent circadian effects on numerous mammalian species, and that given conservation of anatomy and function, the efficacy of light in this range in humans warrants further investigation. We also provide recommendations for the field of chronobiological research, including minimum requirements for the measurement and reporting of light, standardization of terminology (specifically as it pertains to “dim” light), and ideas for reconsidering old data and designing new studies.
Error-Related Activity in Striatal Local Field Potentials and Medial Frontal Cortex: Evidence From Patients With Severe Opioid Abuse Disorder
Authors: Sildatke Elena , Schüller Thomas , Gründler Theo O. J. , Ullsperger Markus , Visser-Vandewalle Veerle , Huys Daniel , Kuhn Jens
Published: February 2021

For successful goal-directed behavior, a performance monitoring system is essential. It detects behavioral errors and initiates behavioral adaptations to improve performance. Two electrophysiological potentials are known to follow errors in reaction time tasks: the error-related negativity (ERN), which is linked to error processing, and the error positivity (Pe), which is associated with subjective error awareness. Furthermore, the correct-related negativity (CRN) is linked to uncertainty about the response outcome. Here we attempted to identify the involvement of the nucleus accumbens (NAc) in the aforementioned performance monitoring processes. To this end, we simultaneously recorded cortical activity (EEG) and local field potentials (LFP) during a flanker task performed by four patients with severe opioid abuse disorder who underwent electrode implantation in the NAc for deep brain stimulation. We observed significant accuracy-related modulations in the LFPs at the time of the ERN/CRN in two patients and at the time of Pe in three patients. These modulations correlated with the ERN in 2/8, with CRN in 5/8 and with Pe in 6/8, recorded channels, respectively. Our results demonstrate the functional interrelation of striatal and cortical processes in performance monitoring specifically related to error processing and subjective error awareness.
Searchlight Classification Informative Region Mixture Model (SCIM): Identification of Cortical Regions Showing Discriminable BOLD Patterns in Event-Related Auditory fMRI Data
Authors: Urbschat Annika , Uppenkamp Stefan , Anemüller Jörn
Published: February 2021

The investigation of abstract cognitive tasks, e.g., semantic processing of speech, requires the simultaneous use of a carefully selected stimulus design and sensitive tools for the analysis of corresponding neural activity that are comparable across different studies investigating similar research questions. Multi-voxel pattern analysis (MVPA) methods are commonly used in neuroimaging to investigate BOLD responses corresponding to neural activation associated with specific cognitive tasks. Regions of significant activation are identified by a thresholding operation during multivariate pattern analysis, the results of which are susceptible to the applied threshold value. Investigation of analysis approaches that are robust to a large extent with respect to thresholding, is thus an important goal pursued here. The present paper contributes a novel statistical analysis method for fMRI experiments, searchlight classification informative region mixture model (SCIM), that is based on the assumption that the whole brain volume can be subdivided into two groups of voxels: spatial voxel positions around which recorded BOLD activity does convey information about the present stimulus condition and those that do not. A generative statistical model is proposed that assigns a probability of being informative to each position in the brain, based on a combination of a support vector machine searchlight analysis and Gaussian mixture models. Results from an auditory fMRI study investigating cortical regions that are engaged in the semantic processing of speech indicate that the SCIM method identifies physiologically plausible brain regions as informative, similar to those from two standard methods as reference that we compare to, with two important differences. SCIM-identified regions are very robust to the choice of the threshold for significance, i.e., less “noisy,” in contrast to, e.g., the binomial test whose results in the present experiment are highly dependent on the chosen significance threshold or random permutation tests that are additionally bound to very high computational costs. In group analyses, the SCIM method identifies a physiologically plausible pre-frontal region, anterior cingulate sulcus, to be involved in semantic processing that other methods succeed to identify only in single subject analyses.
Identification of MicroRNA–Potassium Channel Messenger RNA Interactions in the Brain of Rats With Post-traumatic Epilepsy
Authors: Li Zheng , Ma Yixun , Zhou Fengjuan , Jia Xiao , Zhan Jingjing , Tan Huachao , Wang Xu , Yang Tiantong , Liu Quan
Published: February 2021

Background: Dysregulated expression of microRNAs and potassium channels have been reported for their contributions to seizure onset. However, the microRNA–potassium channel gene interactions in traumatic brain injury-induced post-traumatic epilepsy (PTE) remain unknown.

Methods: PTE was induced in male rats by intracranial injection with ferrous chloride (0.1 mol/L, 1 μl/min) at the right frontal cortex. Electroencephalography was recorded at 60 min, as well as day 1, 7, and 30, and the behavioral seizures were assessed before injection and at different time points after injection. Rats were killed on day 30 after injection. The right frontal cortex samples were collected and subjected to high throughput messenger RNA (mRNA) and microRNA sequencing. A network of differentially expressed potassium channel mRNAs and microRNAs was constructed using OryCun2.0 and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The differential mRNA and microRNA expressions were verified using quantitative real-time-PCR. The microRNA–mRNA was subject to the Pearson correlation analysis.

Results: A PTE rat model was successfully established, as evidenced by behavioral seizures and epileptiform discharges on electroencephalography in PTE rats compared with sham rats. Among the 91 mRNAs and 40 microRNAs that were significantly differentially expressed in the PTE rat brain, 4 mRNAs and 10 microRNAs were associated with potassium channels. Except for potassium calcium-activated channel subfamily N member 2, the other three potassium channel mRNAs were negatively correlated with seven microRNAs. These microRNA–mRNA pairs were enriched in annotations and pathways related to neuronal ion channels and neuroinflammation. Quantitative real-time-PCR and correlation analysis verified negative correlations in miR-449a-5p-KCNH2, miR-98-5p-KCNH2, miR-98-5p-KCNK15, miR-19b-3p-KCNK15, and miR-301a-3p-KCNK15 pairs.

Conclusion: We identified microRNA–potassium channel mRNA interactions associated with PTE, providing potential diagnostic markers and therapeutic targets for PTE.
The Structure and Function of Ionotropic Receptors in Drosophila
Authors: Ni Lina
Published: February 2021

Ionotropic receptors (IRs) are a highly divergent subfamily of ionotropic glutamate receptors (iGluR) and are conserved across Protostomia, a major branch of the animal kingdom that encompasses both Ecdysozoa and Lophothrochozoa. They are broadly expressed in peripheral sensory systems, concentrated in sensory dendrites, and function in chemosensation, thermosensation, and hygrosensation. As iGluRs, four IR subunits form a functional ion channel to detect environmental stimuli. Most IR receptors comprise individual stimulus-specific tuning receptors and one or two broadly expressed coreceptors. This review summarizes the discoveries of the structure of IR complexes and the expression and function of each IR, as well as discusses the future direction for IR studies.
Single-Cell Transcriptomic Reveals Dual and Multi-Transmitter Use in Neurons Across Metazoans
Authors: Brunet Avalos Clarisse , Sprecher Simon G.
Published: February 2021

Neurotransmitter expression is widely used as a criterion for classifying neurons. It was initially thought that neurons express a single type of neurotransmitter, a phenomenon commonly recognized as Dale's principle: “one neuron, one transmitter.” Consequently, the expression of a single neurotransmitter should determine stable and distinguishable neuronal characteristics. However, this notion has been largely challenged and increasing evidence accumulates supporting a different scenario: “one neuron, multiple neurotransmitters.” Single-cell transcriptomics provides an additional path to address coexpression of neurotransmitters, by investigating the expression of genes involved in the biosynthesis and transmission of fast-acting neuromodulators. Here, we study neuronal phenotypes based on the expression of neurotransmitters, at single-cell resolution, across different animal species representing distinct clades of the tree of life. We take advantage of several existing scRNAseq datasets and analyze them in light of neurotransmitter plasticity. Our results show that while most neurons appear to predominantly express a single type of neurotransmitter, a substantial number of neurons simultaneously expresses a combination of them, across all animal species analyzed.