bluuebunny/crossref_metadata_2025 huggingface dataset:
Linear and Non-linear Dynamic Methods Toward Investigating Proprioception Impairment in Non-specific Low Back Pain Patients
Authors: Shokouhyan Seyed Mohammadreza , Davoudi Mehrdad , Hoviattalab Maryam , Abedi Mohsen , Bervis Soha , Parnianpour Mohamad , Brumagne Simon , Khalaf Kinda
Published: November 2020

Central nervous system (CNS) uses vision, vestibular, and somatosensory information to maintain body stability. Research has shown that there is more lumbar proprioception error among low back pain (LBP) individuals as compared to healthy people. In this study, two groups of 20 healthy people and 20 non-specific low back pain (NSLBP) participants took part in this investigation. This investigation focused on somatosensory sensors and in order to alter proprioception, a vibrator (frequency of 70 Hz, amplitude of 0.5 mm) was placed on the soleus muscle area of each leg and two vibrators were placed bilaterally across the lower back muscles. Individuals, whose vision was occluded, were placed on two surfaces (foam and rigid) on force plate, and trunk angles were recorded simultaneously. Tests were performed in eight separate trials; the independent variables were vibration (four levels) and surface (two levels) for within subjects and two groups (healthy and LBP) for between subjects (4 × 2 × 2). MANOVA and multi-factor ANOVA tests were done. Linear parameters for center of pressure (COP) [deviation of amplitude, deviation of velocity, phase plane portrait (PPP), and overall mean velocity] and non-linear parameters for COP and trunk angle [recurrence quantification analysis (RQA) and Lyapunov exponents] were chosen as dependent variables. Results indicated that NSLBP individuals relied more on ankle proprioception for postural stability. Similarly, RQA parameters for the COP on both sides and for the trunk sagittal angle indicated more repeated patterns of movement among the LBP cohort. Analysis of short and long Lyapunov exponents showed that people with LBP caused no use of all joints in their bodies (non-flexible), are less stable than healthy subjects.
GFOGER Peptide Modifies the Protein Content of Extracellular Vesicles and Inhibits Vascular Calcification
Authors: Mansour Ali , Darwiche Walaa , Yaker Linda , Da Nascimento Sophie , Gomila Cathy , Rossi Claire , Jung Vincent , Sonnet Pascal , Kamel Saïd , Guerrera Ida Chiara , Boullier Agnès , Ausseil Jérôme
Published: November 2020

Objective

Vascular calcification (VC) is an active process during which vascular smooth muscle cells (VSMCs) undergo an osteogenic switch and release extracellular vesicles (EVs). In turn, the EVs serve as calcification foci via interaction with type 1 collagen (COL1). We recently showed that a specific, six-amino-acid repeat (GFOGER) in the sequence of COL1 was involved in the latter’s interaction with integrins expressed on EVs. Our main objective was to test the GFOGER ability to inhibit VC.

Approach

We synthesized the GFOGER peptide and tested its ability to inhibit the inorganic phosphate (Pi)-induced calcification of VSMCs and aortic rings. Using mass spectrometry, we studied GFOGER’s effect on the protein composition of EVs released from Pi-treated VSMCs.

Results

Calcification of mouse VSMCs (MOVAS-1 cells), primary human VSMCs, and rat aortic rings was lower in the presence of GFOGER than with Pi alone (with relative decreases of 66, 58, and 91%, respectively; p < 0.001 for all) (no effect was observed with the scramble peptide GOERFG). A comparative proteomic analysis of EVs released from MOVAS-1 cells in the presence or absence of Pi highlighted significant differences in EVs’ protein content. Interestingly, the expression of some of the EVs’ proteins involved in the calcification process (such as osteogenic markers, TANK-binding kinase 1, and casein kinase II) was diminished in the presence of GFOGER peptide (data are available via ProteomeXchange with identifier PXD018169∗). The decrease of osteogenic marker expression observed in the presence of GFOGER was confirmed by q-RT-PCR analysis.

Conclusion

GFOGER peptide reduces vascular calcification by modifying the protein content of the subsequently released EVs, in particular by decreasing osteogenicswitching in VSMCs.
Cadmium-Induced Cytotoxicity: Effects on Mitochondrial Electron Transport Chain
Authors: Branca Jacopo Junio Valerio , Pacini Alessandra , Gulisano Massimo , Taddei Niccolò , Fiorillo Claudia , Becatti Matteo
Published: November 2020

Cadmium (Cd) is a well-known heavy metal and environmental toxicant and pollutant worldwide, being largely present in every kind of item such as plastic (toys), battery, paints, ceramics, contaminated water, air, soil, food, fertilizers, and cigarette smoke. Nowadays, it represents an important research area for the scientific community mainly for its effects on public health. Due to a half-life ranging between 15 and 30 years, Cd owns the ability to accumulate in organs and tissues, exerting deleterious effects. Thus, even at low doses, a Cd prolonged exposure may cause a multiorgan toxicity. Mitochondria are key intracellular targets for Cd-induced cytotoxicity, but the underlying mechanisms are not fully elucidated. The present review is aimed to clarify the effects of Cd on mitochondria and, particularly, on the mitochondrial electron transport chain.
A Screen-Printed Electrode Modified With Graphene/Co3O4 Nanocomposite for Electrochemical Detection of Tramadol
Authors: Aflatoonian Mohammad Reza , Tajik Somayeh , Aflatoonian Behnaz , Beitollahi Hadi , Zhang Kaiqiang , Le Quyet Van , Cha Joo Hwan , Jang Ho Won , Shokouhimehr Mohammadreza , Peng Wanxi
Published: November 2020

In this paper, graphene (Gr)/Co3O4 nanocomposite was synthesized and utilized for the development of a novel electrochemical sensor to detect tramadol. Tramadol determination was examined by linear sweep voltammetry, differential pulse voltammetry, cyclic voltammetry, and chronoamperometry on Gr/Co3O4 nanocomposite-modified screen-printed electrode (Gr/Co3O4/SPE) in phosphate-buffered saline (PBS). Under the optimized condition, the detection limit of tramadol is 0.03 μM (S/N = 3) in the linear ranges of 0.1–500.0 μM. Furthermore, Gr/Co3O4/SPE was satisfactorily utilized to detect tramadol in tramadol tablet and urine specimens.
Fungi vs. Fungi in Biocontrol: An Overview of Fungal Antagonists Applied Against Fungal Plant Pathogens
Authors: Thambugala Kasun M. , Daranagama Dinushani A. , Phillips Alan J. L. , Kannangara Sagarika D. , Promputtha Itthayakorn
Published: November 2020

Plant pathogens cause severe losses or damage to crops worldwide and thereby significantly reduce the quality and quantity of agricultural commodities. World tendencies are shifting towards reducing the usage of chemically synthesized pesticides, while various biocontrol methods, strategies and approaches are being used in plant disease management. Fungal antagonists play a significant role in controlling plant pathogens and diseases and they are used as Biocontrol Agents (BCAs) throughout the world. This review provides a comprehensive list of fungal BCAs used against fungal plant pathogens according to modern taxonomic concepts, and clarifies their phylogenetic relationships because thewrong names are frequently used in the literature of biocontrol. Details of approximately 300 fungal antagonists belonging to 13 classes and 113 genera are listed together with the target pathogens and corresponding plant diseases. Trichoderma is identified as the genus with greatest potential comprising 25 biocontrol agents that have been used against a number of plant fungal diseases. In addition to Trichoderma, nine genera are recognized as significant comprising five or more known antagonistic species, namely, Alternaria, Aspergillus, Candida, Fusarium, Penicillium, Pichia, Pythium, Talaromyces, and Verticillium. A phylogenetic analysis based on partial sequences of the 28S nrRNA gene (LSU) of fungal antagonists was performed to establish their phylogenetic relationships.
Coming to GRIPs With NETs Discourse: Implications of Discursive Structures for Emerging Governance of Negative Emissions Technologies in the UK
Authors: Boettcher Miranda
Published: November 2020

As the international community rallies around Net-Zero emissions targets, there is increasing interest in the development of governance for Negative Emissions Technologies (NETs), a range of proposed approaches which involve removing greenhouse gases from the atmosphere. It has been pointed out that the governance development process should include “opening up” the discussion of NETs governance, moving the debate beyond the bounds of technocratic, neoliberal discourse and thereby paving the way for more responsible, inclusive governance of technologies. The implication is that there is a constitutive and qualitative link between discourse and governance – that governance development is shaped by discourse. However, so far there has been limited work done to link empirical mapping of the discursive structures in different spheres of the NETs debate to theoretically-informed anticipation of how these structures may influence governance development. This paper presents a sociology-of-knowledge (SKAD) discourse analysis of a series of interviews with UK representatives from the industry/policy interface about what they consider to be appropriate governance instruments for NETs. Linking discursive structures to governance development using the concept of governmentality, the paper critically discusses how a set of political, economic and ethical discursive structures currently underpinning the industry and policy spheres of the UK NETs debate may be shaping governance development. The paper shows what types of discourse/knowledge and social actors are being privileged/excluded within the structure of the UK NETs debate, and highlights ways in which discursive mapping can play a key emancipatory role in “opening up” governance development processes.
The Regulatory Role of Histone Modification on Gene Expression in the Early Stage of Myocardial Infarction
Authors: Wang Jinyu , Lin Bowen , Zhang Yanping , Ni Le , Hu Lingjie , Yang Jian , Xu Liang , Shi Dan , Chen Yi-Han
Published: November 2020

Myocardial infarction (MI) is a fatal heart disease with high morbidity and mortality. Various studies have demonstrated that a series of relatively specific biological events occur within 24 h of MI. However, the roles of histone modifications in this pathological process are still poorly understood. To investigate the regulation of histone modifications on gene expression in early MI, we performed RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) on myocardial tissues 24 h after the onset of MI. The genome-wide profiles of five histone marks (H3K27ac, H3K9ac, H3K4me3, H3K9me3, and H3K27me3) were explored through ChIP-seq. RNA-seq identified 1,032 differentially expressed genes (DEGs) between the MI and sham groups. ChIP-seq analysis found that 195 upregulated DEGs were modified by change of at least one of the three active histone marks (H3K27ac, H3K9ac, and H3K4me3), and the biological processes and pathways analysis showed that these DEGs were significantly enriched in cardiomyocyte differentiation and development, inflammation, angiogenesis, and metabolism. In the transcriptional regulatory network, Ets1, Etv1, and Etv2 were predicted to be involved in gene expression regulation. In addition, by integrating super-enhancers (SEs) with RNA-seq data, 76 DEGs were associated with H3K27ac-enriched SEs in the MI group, and the functions of these SE-associated DEGs were mainly related to angiogenesis. Our results suggest that histone modifications may play important roles in the regulation of gene expression in the early stage of MI, and the early angiogenesis response may be initiated by SEs.
Preliminary Evaluation of the Engagement and Effectiveness of a Mental Health Chatbot
Authors: Daley Kate , Hungerbuehler Ines , Cavanagh Kate , Claro Heloísa Garcia , Swinton Paul Alan , Kapps Michael
Published: November 2020

Background: Mental health difficulties are highly prevalent, yet access to support is limited by barriers of stigma, cost, and availability. These issues are even more prevalent in low- and middle-income countries, and digital technology is one potential way to overcome these barriers. Digital mental health interventions are effective but often struggle with low engagement rates, particularly in the absence of human support. Chatbots could offer a scalable solution, simulating human support at a lower cost.

Objective: To complete a preliminary evaluation of engagement and effectiveness of Vitalk, a mental health chatbot, at reducing anxiety, depression and stress.

Methods: Real world data was analyzed from 3,629 Vitalk users who had completed the first phase of a Vitalk program (“less anxiety,” “less stress” or “better mood”). Programs were delivered through written conversation with a chatbot. Engagement was calculated from the number of responses sent to the chatbot divided by days in the program.

Results: Users sent an average of 8.17 responses per day. For all three programs, target outcome scores reduced between baseline and follow up with large effect sizes for anxiety (Cohen's d = −0.85), depression (Cohen's d = −0.91) and stress (Cohen's d = −0.81). Increased engagement resulted in improved post-intervention values for anxiety and depression.

Conclusion: This study highlights a chatbot's potential to reduce mental health symptoms in the general population within Brazil. While findings show promise, further research is required.
Complement C1q as a Potential Biomarker for Obesity and Metabolic Syndrome in Chinese Adolescents
Authors: Yang Xuelian , Ma Yanan , Zhao Zhongyi , Zhen Shihan , Wen Deliang
Published: November 2020

Background

Complement C1q (C1q) has been confirmed to be related to obesity, metabolic syndrome (MetS), and its components. However, human data regarding the associations are relatively scarce. This study aimed to investigate associations of C1q with obesity as well as MetS in Chinese adolescents.

Methods

A total of 1,191 Chinese adolescents aged 13–18 years were enrolled in this study. The biochemical and anthropometric variables of all the subjects were evaluated using standardized procedures. C1q was measured using the immunoturbidometric assay. The relationship between C1q and obesity or MetS was analyzed using multiple regression analyses.

Results

Obesity was more prevalent among participants in the highest tertile than in the lowest tertile of C1q levels. The highest tertile of C1q was related to a greater effect on the risk of MetS, and its trend test was statistically significant. Except for hyperglycemia, the prevalence of other components of MetS significantly increased relative to an increase in C1q tertile. Receiver operating characteristic (ROC) curve analysis of C1q for predicting adolescents with MetS illustrated that the area under the curve (AUC) was 0.82 [95% confidence interval (CI): 0.76, 0.88; P<0.001] in the total population after adjusting for confounders.

Conclusions

This study observed a significantly higher prevalence of obesity and MetS features in adolescents with high C1q. The findings of the current study also reported a significant relationship between C1q levels and MetS components [except for fasting plasma glucose (FPG)] in Chinese adolescents. C1q may represent a biomarker for predicting obesity or MetS in adolescents.
How Thermodynamics Illuminates Population Interactions in Microbial Communities
Authors: Seto Mayumi , Iwasa Yoh
Published: November 2020

In traditional population models of microbial ecology, there are two central players: producers and consumers (including decomposers that depend on organic carbon). Producers support surface ecosystems by generating adenosine triphosphate (ATP) from sunlight, part of which is used to build new biomass from carbon dioxide. In contrast, the productivity of subsurface ecosystems with a limited supply of sunlight must rely on bacteria and archaea that are able generate ATP solely from chemical or electric energy to fix inorganic carbon. These “light-independent producers” are frequently not included in traditional food webs, even though they are ubiquitous in nature and interact with one another through the utilization of the by-products of others. In this review, we introduce theoretical approaches based on population dynamics that incorporate thermodynamics to highlight characteristic interactions in the microbial community of subsurface ecosystems, which may link community structures and ecosystem expansion under conditions of a limited supply of sunlight. In comparison with light-dependent producers, which compete with one another for light, the use of Gibbs free energy (chemical energy) can lead cooperative interactions among light-independent producers through the effects of the relative quantities of products and reactants on the available chemical energy, which is termed abundant resource premium. The development of a population theory that incorporates thermodynamics offers fundamental ecological insights into subsurface microbial ecosystems, which may be applied to fields of study such as environmental science/engineering, astrobiology, or the microbial ecosystems of the early earth.
Methodologies and Challenges for CRISPR/Cas9 Mediated Genome Editing of the Mammalian Brain
Authors: Nishizono Hirofumi , Yasuda Ryohei , Laviv Tal
Published: November 2020

Neurons and glia are highly polarized cells with extensive subcellular structures extending over large distances from their cell bodies. Previous research has revealed elaborate protein signaling complexes localized within intracellular compartments. Thus, exploring the function and the localization of endogenous proteins is vital to understanding the precise molecular mechanisms underlying the synapse, cellular, and circuit function. Recent advances in CRISPR/Cas9-based genome editing techniques have allowed researchers to rapidly develop transgenic animal models and perform single-cell level genome editing in the mammalian brain. Here, we introduce and comprehensively review the latest techniques for genome-editing in whole animals using fertilized eggs and methods for gene editing in specific neuronal populations in the adult or developing mammalian brain. Finally, we describe the advantages and disadvantages of each technique, as well as the challenges that lie ahead to advance the generation of methodologies for genome editing in the brain using the current CRISPR/Cas9 system.
Effects of Genetic Polymorphisms of Drug Transporter ABCB1 (MDR1) and Cytochrome P450 Enzymes CYP2A6, CYP2B6 on Nicotine Addiction and Smoking Cessation
Authors: Muderrisoglu Ahmet , Babaoglu Elif , Korkmaz Elif Tugce , Ongun Mert C. , Karabulut Erdem , Iskit Alper B. , Emri Salih , Babaoglu Melih O.
Published: November 2020

Objectives

To determine the effects of genetic polymorphisms of ABCB1 (MDR1), CYP2A6, CYP2B6 on smoking status, and clinical outcomes of smoking cessation therapies in a Turkish population.

Methods

130 smokers and 130 non-smokers were recruited. Individuals who never smoked were described as non-smokers. 130 smokers were treated with nicotine replacement therapy (NRT) (n = 40), bupropion (n = 47), bupropion + NRT (n = 15), and varenicline (n = 28). Smokers were checked by phone after 12 weeks of treatment whether they were able to quit smoking or not. Genotyping and phenotyping were performed.

Results

Cessation rates were as follows; 20.0% for NRT, 29.8% for bupropion, 40.0% for bupropion + NRT, 57.1% for varenicline (p = 0.013). The frequency of ABCB1 1236TT-2677TT-3435TT haplotype was significantly higher in non-smokers as compared to smokers (21.5% vs. 10.8, respectively; p = 0.018). Neither smoking status nor smoking cessation rates were associated with genetic variants of CYP2A6 (p = 0.652, p = 0.328, respectively), or variants of CYP2B6 (p = 0.514, p = 0.779, respectively).

Conclusion

Genetic variants of the drug transporter ABCB1 and the 1236TT-2677TT-3435TT haplotype was significantly associated with non-smoking status. Neither ABCB1 nor CYP2A6, CYP2B6 genetic variants were associated with smoking cessation rates at the 12th week of drug treatment.
Integrative Analysis of Genomics and Transcriptome Data to Identify Regulation Networks in Female Osteoporosis
Authors: Zhang Xianzuo , Chen Kun , Chen Xiaoxuan , Kourkoumelis Nikolaos , Li Guoyuan , Wang Bing , Zhu Chen
Published: November 2020

Background: Osteoporosis is a highly heritable skeletal muscle disease. However, the genetic mechanisms mediating the pathogenesis of osteoporosis remain unclear. Accordingly, in this study, we aimed to clarify the transcriptional regulation and heritability underlying the onset of osteoporosis.

Methods: Transcriptome gene expression data were obtained from the Gene Expression Omnibus database. Microarray data from peripheral blood monocytes of 73 Caucasian women with high and low bone mineral density (BMD) were analyzed. Differentially expressed messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) were identified. Differences in BMD were then attributed to several gene modules using weighted gene co-expression network analysis (WGCNA). LncRNA/mRNA regulatory networks were constructed based on the WGCNA and subjected to functional enrichment analysis.

Results: In total, 3,355 mRNAs and 999 lncRNAs were identified as differentially expressed genes between patients with high and low BMD. The WGCNA yielded three gene modules, including 26 lncRNAs and 55 mRNAs as hub genes in the blue module, 36 lncRNAs and 31 mRNAs as hub genes in the turquoise module, and 56 mRNAs and 30 lncRNAs as hub genes in the brown module. JUN and ACSL5 were subsequently identified in the modular gene network. After functional pathway enrichment, 40 lncRNAs and 16 mRNAs were found to be related to differences in BMD. All three modules were enriched in metabolic pathways. Finally, mRNA/lncRNA/pathway networks were constructed using the identified regulatory networks of lncRNAs/mRNAs and pathway enrichment relationships.

Conclusion: The mRNAs and lncRNAs identified in this WGCNA could be novel clinical targets in the diagnosis and management of osteoporosis. Our findings may help elucidate the complex interactions between transcripts and non-coding RNAs and provide novel perspectives on the regulatory mechanisms of osteoporosis.
Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight
Authors: Andreone Sara , Gambardella Adriana Rosa , Mancini Jacopo , Loffredo Stefania , Marcella Simone , La Sorsa Valentina , Varricchi Gilda , Schiavoni Giovanna , Mattei Fabrizio
Published: November 2020

Interleukin-33 (IL-33) is an epithelial-derived cytokine that can be released upon tissue damage, stress, or infection, acting as an alarmin for the immune system. IL-33 has long been studied in the context of Th2-related immunopathologies, such as allergic diseases and parasitic infections. However, its capacity to stimulate also Th1-type of immune responses is now well established. IL-33 binds to its specific receptor ST2 expressed by most immune cell populations, modulating a variety of responses. In cancer immunity, IL-33 can display both pro-tumoral and anti-tumoral functions, depending on the specific microenvironment. Recent findings indicate that IL-33 can effectively stimulate immune effector cells (NK and CD8+ T cells), eosinophils, basophils and type 2 innate lymphoid cells (ILC2) promoting direct and indirect anti-tumoral activities. In this review, we summarize the most recent advances on anti-tumor immune mechanisms operated by IL-33, including the modulation of immune checkpoint molecules, with the aim to understand its potential as a therapeutic target in cancer.
Redox Regulator GLRX Is Associated With Tumor Immunity in Glioma
Authors: Chang Yuanhao , Li Guanzhang , Zhai You , Huang Lijie , Feng Yuemei , Wang Di , Zhang Wei , Hu Huimin
Published: November 2020

Glutaredoxin is central to cellular redox chemistry and regulates redox homeostasis and malignant progression of many cancers. In glioma, the role of its coding gene (GLRX) remains unclear. We aimed to elucidate the role of glutaredoxin at the transcriptome level and its clinical prognostic value in glioma. In total, we evaluated 1,717 glioma samples with transcriptome data and corresponding clinical data as well as single-cell sequencing data from 6 glioma patients from publicly available databases. Gene set variation analysis and gene ontology analysis were performed to reveal the biological function of GLRX. The immune cell enrichment score was calculated by GSVA analysis. Single-cell sequencing data was visualized by t-distributed stochastic neighbor embedding analysis. The prognostic value of GLRX in glioma was verified by the Kaplan-Meier curve and multivariate COX analysis. GLRX was found to be highly enriched in gliomas of higher grades with wild-type IDH, without 1p/19q co-deletion, and with a methylated MGMT promoter. Moreover, GLRX could be a potential marker for the mesenchymal molecular subtype of gliomas. The expression of GLRX was closely related to the tumor immune process, immune checkpoints, and inflammatory factors with GLRX being specifically expressed in M0 macrophages. GLRX is also shown to be an independent prognostic factor in glioma. Altogether, our study outcomes show that GLRX is highly enriched in malignant gliomas and is closely related to the tumor immune microenvironment. Therefore, GLRX-targeted cell redox regulatory therapy may enhance the efficacy of glioma immunotherapy.
MAIT Cells in Barrier Tissues: Lessons from Immediate Neighbors
Authors: Amini Ali , Pang Declan , Hackstein Carl-Philipp , Klenerman Paul
Published: November 2020

Mucosal-associated invariant T (MAIT) cells are innate-like T cells present at considerable frequencies in human blood and barrier tissues, armed with an expanding array of effector functions in response to homeostatic perturbations. Analogous to other barrier immune cells, their phenotype and function is driven by crosstalk with host and dynamic environmental factors, most pertinently the microbiome. Given their distribution, they must function in diverse extracellular milieus. Tissue-specific and adapted functions of barrier immune cells are shaped by transcriptional programs and regulated through a blend of local cellular, inflammatory, physiological, and metabolic mediators unique to each microenvironment. This review compares the phenotype and function of MAIT cells with other barrier immune cells, highlighting potential areas for future exploration. Appreciation of MAIT cell biology within tissues is crucial to understanding their niche in health and disease.
Systemic CD4 Immunity as a Key Contributor to PD-L1/PD-1 Blockade Immunotherapy Efficacy
Authors: Zuazo Miren , Arasanz Hugo , Bocanegra Ana , Fernandez Gonzalo , Chocarro Luisa , Vera Ruth , Kochan Grazyna , Escors David
Published: November 2020

PD-L1/PD-1 blockade immunotherapy has significantly improved treatment outcome for several cancer types compared to conventional cytotoxic therapies. However, the specific molecular and cellular mechanisms behind its efficacy are currently unclear. There is increasing evidence in murine models and in patients that unveil the key importance of systemic immunity to achieve clinical responses under several types of immunotherapy. Indeed, PD-L1/PD-1 blockade induces the expansion of systemic CD8+ PD-1+ T cell subpopulations which might be responsible for direct anti-tumor responses. However, the role of CD4+ T cells in PD-L1/PD-1 blockade-induced anti-tumor responses has been less documented. In this review we focus on the experimental data supporting the “often suspected” indispensable helper function of CD4 T cells towards CD8 effector anti-tumor responses in cancer; and particularly, we highlight the recently published studies uncovering the key contribution of systemic CD4 T cells to clinical efficacy in PD-L1/PD-1 blockade therapies. We conclude and propose that the presence of specific CD4 T cell memory subsets in peripheral blood before the initiation of treatments is a strong predictor of responses in non-small cell lung cancer patients. Therefore, development of new approaches to improve CD4 responses before PD-L1/PD-1 blockade therapy could be the solution to increase response rates and survival of patients.
Granulocytic Myeloid-Derived Suppressor Cell Exosomal Prostaglandin E2 Ameliorates Collagen-Induced Arthritis by Enhancing IL-10+ B Cells
Authors: Wu Xinyu , Zhu Dongwei , Tian Jie , Tang Xinyi , Guo Hongye , Ma Jie , Xu Huaxi , Wang Shengjun
Published: November 2020

The results of recent studies have shown that granulocytic-myeloid derived suppressor cells (G-MDSCs) can secrete exosomes that transport various biologically active molecules with regulatory effects on immune cells. However, their roles in autoimmune diseases such as rheumatoid arthritis remain to be further elucidated. In the present study, we investigated the influence of exosomes from G-MDSCs on the humoral immune response in murine collagen-induced arthritis (CIA). G-MDSCs exosomes-treated mice showed lower arthritis index values and decreased inflammatory cell infiltration. Treatment with G-MDSCs exosomes promoted splenic B cells to secrete IL-10 both in vivo and in vitro. In addition, a decrease in the proportion of plasma cells and follicular helper T cells was observed in drainage lymph nodes from G-MDSCs exosomes-treated mice. Moreover, lower serum levels of IgG were detected in G-MDSCs exosomes-treated mice, indicating an alteration of the humoral environment. Mechanistic studies showed that exosomal prostaglandin E2 (PGE2) produced by G-MDSCs upregulated the phosphorylation levels of GSK-3β and CREB, which play a key role in the production of IL-10+ B cells. Taken together, our findings demonstrated that G-MDSC exosomal PGE2 attenuates CIA in mice by promoting the generation of IL-10+ Breg cells.
Case Report: All That Glisters Is Not* Cancer
Authors: Tirelli Claudio , Bortolotto Chandra , Morbini Patrizia , Stella Giulia Maria
Published: November 2020

Properly performed staging in non-small-cell lung cancer (NSCLC) is necessary to avoid wrong therapeutic decisions. Here we present a case which manifested as advanced NSCLC but ultimately was composed of two different and rare pathologies. The first is a TTF-1 positive axillary lymph node that could be defined either as an unusual isolated differentiated cancer of unknown primary or as an even rarer case of ectopic lung epithelium which underwent malignant transformation. The second is sarcoidosis, a sarcoid-like alteration, in remission after oral steroids. The main implication of a correct diagnosis regards patient outcome and the avoidance of toxic inappropriate systemic chemotherapy.
Rhizosphere Bacterial Community Response to Continuous Cropping of Tibetan Barley
Authors: Yao Youhua , Yao Xiaohua , An Likun , Bai Yixiong , Xie Deqing , Wu Kunlun
Published: November 2020

Long-term continuous cropping influences the nutrient of soil and microbiome of the rhizosphere, resulting in the yield decrease of crops. Tibetan barley is a dominant cereal crop cultivated at high altitudes in Tibet. Its growth and yield are negatively affected by continuous cropping; however, the response of the rhizosphere microbial community to continuous cropping remains poorly understood. To address this question, we investigated the bacterial community structure and conducted predictive functional profiling on rhizosphere soil from Tibetan barley monocropped for 2–6 years. The results revealed that long-term continuous cropping markedly decreased total nitrogen and available nitrogen in rhizosphere soil. Illumina high-throughput sequencing of 16S rRNA genes indicated that the bacterial community was altered by continuous cropping; operational taxonomic units (OTUs), Shannon index, and Faith Phylogenetic Diversity decreased with increasing monocropping duration. Relative abundances of family Pseudomonadaceae, Cytophagaceae, and Nocardioidaceae were significantly increased, while those of Chitinophagaceae and Sphingomonadaceae were significantly decreased (all p < 0.05). Besides, continuous cropping significantly increased the abundance of bacteria associated with chemoheterotrophy, aromatic compound degradation, and nitrate reduction (p < 0.05). Generalized boosted regression model analysis indicated that total nitrogen was the most important contributor to the bacterial community diversity, indicating their roles in shaping the rhizosphere bacterial community during continuous cropping. Overall, continuous cropping had a significant impact on the structure of bacterial communities in rhizosphere soil of Tibetan barley, and these results will improve our understanding of soil bacterial community regulation and soil health maintenance in Tibetan barley farm systems.
Alterations and Correlations in Microbial Community and Metabolome Characteristics in Generalized Aggressive Periodontitis
Authors: Shi Meng , Wei Yiping , Nie Yong , Wang Cui , Sun Fei , Jiang Wenting , Hu Wenjie , Wu Xiaolei
Published: November 2020

This study aimed to characterize the microbial community and metabolic profiles in generalized aggressive periodontitis (AgP) using 16S ribosomal RNA (rRNA) gene high-throughput sequencing and gas chromatography-mass spectrometry (GC-MS). A total of 146 subgingival plaque samples and 50 gingival crevicular fluid (GCF) samples were collected from 24 patients with AgP and 10 periodontally healthy subjects (PH). Striking differences were observed in subgingival microbiome and GCF metabolomics between patients with AgP and PH, but not between samples with different probing depths (PDs). Metabolomics analysis combined with enrichment analysis showed that periodontitis significantly altered the concentration of compounds associated with biosynthesis of amino acids (e.g., alanine, leucine, isoleucine, and valine), galactose metabolism (e.g., myo-inositol, galactose, glucose, and hexitol), and pyrimidine metabolism (e.g., uracil, uridine, beta alanine, and thymine). Correlation analysis showed that the genera with significant difference between AgP and PH were usually significantly correlated with more metabolites, such asAggregatibacter,Rothia,Peptostreptococcaceae_[XI][G-5], andBacteroidaceae_[G-1]. While glucose and oxoproline had the most significant correlations with microorganisms. Our results revealed distinct microbial communities and metabolic profiles between AgP and PH. The significant correlation between microbial taxa and metabolites suggested the possible mechanisms for periodontitis. Our results also provided effective approaches for detecting periodontal disease and managing periodontitis.
Comparative Genomic Analyses Reveal a Specific Mutation Pattern Between Human Coronavirus SARS-CoV-2 and Bat-CoV RaTG13
Authors: Lv Longxian , Li Gaolei , Chen Jinhui , Liang Xinle , Li Yudong
Published: November 2020

Background

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, rapidly grew into a global pandemic. How SARS-CoV-2 evolved remains unclear.

Methods

We performed a comprehensive analysis using the available genomes of SARS-CoV-2 and its closely related coronaviruses.

Results

The ratio of nucleotide substitutions to amino acid substitutions of the spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-CoV RaTG13 was markedly higher than that between other coronaviruses (range, 1.29–4.81); the ratio of non-synonymous to synonymous substitution rates (dN/dS) between SARS-CoV-2 WIV04 and Bat-CoV RaTG13 was the lowest among all the performed comparisons, suggesting evolution under stringent selective pressure. Notably, the relative proportion of the T:C transition was markedly higher between SARS-CoV-2 WIV04 and Bat-CoV RaTG13 than between other compared coronaviruses. Codon usage is similar across these coronaviruses and is unlikely to explain the increased number of synonymous mutations. Moreover, some sites of the spike protein might be subjected to positive selection.

Conclusions

Our results showed an increased proportion of synonymous substitutions and the T:C transition between SARS-CoV-2 and RaTG13. Further investigation of the mutation pattern mechanism would contribute to understanding viral pathogenicity and its adaptation to hosts.
The Network of Interactions Between Classical Swine Fever Virus Nonstructural Protein p7 and Host Proteins
Authors: Fan Jindai , Zhang Mengru , Liu Chenchen , Zhu Mengjiao , Zhang Zilin , Wu Keke , Li Zhaoyao , Li Wenhui , Fan Shuangqi , Ju Chunmei , Yi Lin , Ding Hongxing , Zhao Mingqiu , Chen Jinding
Published: November 2020

Classical swine fever (CSF) is a highly contagious viral disease causing severe economic losses to the swine industry. As viroporins of viruses modulate the cellular ion balance and then take over the cellular machinery, blocking the activity of viroporin or developing viroporin-defective attenuated vaccines offers new approaches to treat or prevent viral infection. Non-structural protein p7 of CSF virus (CSFV) is a viroporin, which was highly involved in CSFV virulence. Deciphering the interaction between p7 and host proteins will aid our understanding of the mechanism of p7-cellular protein interaction affecting CSFV replication. In the present study, seven host cellular proteins including microtubule-associated protein RP/EB family member 1 (MAPRE1), voltage-dependent anion channel 1 (VDAC1), proteasome maturation protein (POMP), protein inhibitor of activated STAT 1 (PIAS1), gametogenetin binding protein 2 (GGNBP2), COP9 signalosome subunit 2 (COPS2), and contactin 1 (CNTN1) were identified as the potential interactive cellular proteins of CSFV p7 by using yeast two-hybrid (Y2H) screening. Plus, the interaction of CSFV p7 with MAPRE1 and VDAC1 was further evaluated by co-immunoprecipitation and GST-pulldown assay. Besides, the p7-cellular protein interaction network was constructed based on these seven host cellular proteins and the STRING database. Enrichment analysis of GO and KEGG indicated that many host proteins in the p7-cellular protein interaction network were mainly related to the ubiquitin-proteasome system, cGMP-PKG signaling pathway, calcium signaling pathway, and JAK-STAT pathway. Overall, this study identified potential interactive cellular proteins of CSFV p7, constructed the p7-cellular protein interaction network, and predicted the potential pathways involved in the interaction between CSFV p7 and host cells.
A Comparative Study of the Innate Humoral Immune Response to Avian Influenza Virus in Wild and Domestic Mallards
Authors: van Dijk Jacintha G. B. , Verhagen Josanne H. , Hegemann Arne , Tolf Conny , Olofsson Jenny , Järhult Josef D. , Waldenström Jonas
Published: November 2020

Domestic mallards (Anas platyrhynchos domesticus) are traditionally used as a model to investigate infection dynamics and immune responses to low pathogenic avian influenza viruses (LPAIVs) in free-living mallards. However, it is unclear whether the immune response of domestic birds reflects the response of their free-living counterparts naturally exposed to these viruses. We investigated the extent to which the innate humoral immune response was similar among (i) wild-type domestic mallards in primary and secondary infection with LPAIV H4N6 in a laboratory setting (laboratory mallards), (ii) wild-type domestic mallards naturally exposed to LPAIVs in a semi-natural setting (sentinel mallards), and (iii) free-living mallards naturally exposed to LPAIVs. We quantified innate humoral immune function by measuring non-specific natural antibodies (agglutination), complement activity (lysis), and the acute phase protein haptoglobin. We demonstrate that complement activity in the first 3 days after LPAIV exposure was higher in primary-exposed laboratory mallards than in sentinel and free-living mallards. LPAIV H4N6 likely activated the complement system and the acute phase response in primary-exposed laboratory mallards, as lysis was higher and haptoglobin lower at day 3 and 7 post-exposure compared to baseline immune function measured prior to exposure. There were no differences observed in natural antibody and haptoglobin concentrations among laboratory, sentinel, and free-living mallards in the first 3 days after LPAIV exposure. Our study demonstrates that, based on the three innate humoral immune parameters measured, domestic mallards seem an appropriate model to investigate innate immunology of their free-living counterparts, albeit the innate immune response of secondary-LPAIV exposed mallards is a better proxy for the innate immune response in pre-exposed free-living mallards than that of immunologically naïve mallards.
DNNBrain: A Unifying Toolbox for Mapping Deep Neural Networks and Brains
Authors: Chen Xiayu , Zhou Ming , Gong Zhengxin , Xu Wei , Liu Xingyu , Huang Taicheng , Zhen Zonglei , Liu Jia
Published: November 2020

Deep neural networks (DNNs) have attained human-level performance on dozens of challenging tasks via an end-to-end deep learning strategy. Deep learning allows data representations that have multiple levels of abstraction; however, it does not explicitly provide any insights into the internal operations of DNNs. Deep learning's success is appealing to neuroscientists not only as a method for applying DNNs to model biological neural systems but also as a means of adopting concepts and methods from cognitive neuroscience to understand the internal representations of DNNs. Although general deep learning frameworks, such as PyTorch and TensorFlow, could be used to allow such cross-disciplinary investigations, the use of these frameworks typically requires high-level programming expertise and comprehensive mathematical knowledge. A toolbox specifically designed as a mechanism for cognitive neuroscientists to map both DNNs and brains is urgently needed. Here, we present DNNBrain, a Python-based toolbox designed for exploring the internal representations of DNNs as well as brains. Through the integration of DNN software packages and well-established brain imaging tools, DNNBrain provides application programming and command line interfaces for a variety of research scenarios. These include extracting DNN activation, probing and visualizing DNN representations, and mapping DNN representations onto the brain. We expect that our toolbox will accelerate scientific research by both applying DNNs to model biological neural systems and utilizing paradigms of cognitive neuroscience to unveil the black box of DNNs.
Lesion Induced Error on Automated Measures of Brain Volume: Data From a Pediatric Traumatic Brain Injury Cohort
Authors: King Daniel J. , Novak Jan , Shephard Adam J. , Beare Richard , Anderson Vicki A. , Wood Amanda G.
Published: November 2020

Structural segmentation of T1-weighted (T1w) MRI has shown morphometric differences, both compared to controls and longitudinally, following a traumatic brain injury (TBI). While many patients with TBI present with abnormalities on structural MRI images, most neuroimaging software packages have not been systematically evaluated for accuracy in the presence of these pathology-related MRI abnormalities. The current study aimed to assess whether acute MRI lesions (MRI acquired 7–71 days post-injury) cause error in the estimates of brain volume produced by the semi-automated segmentation tool, Freesurfer. More specifically, to investigate whether this error was global, the presence of lesion-induced error in the contralesional hemisphere, where no abnormal signal was present, was measured. A dataset of 176 simulated lesion cases was generated using actual lesions from 16 pediatric TBI (pTBI) cases recruited from the emergency department and 11 typically-developing controls. Simulated lesion cases were compared to the “ground truth” of the non-lesion control-case T1w images. Using linear mixed-effects models, results showed that hemispheric measures of cortex volume were significantly lower in the contralesional-hemisphere compared to the ground truth. Interestingly, however, cortex volume (and cerebral white matter volume) were not significantly different in the lesioned hemisphere. However, percent volume difference (PVD) between the simulated lesion and ground truth showed that the magnitude of difference of cortex volume in the contralesional-hemisphere (mean PVD = 0.37%) was significantly smaller than that in the lesioned hemisphere (mean PVD = 0.47%), suggesting a small, but systematic lesion-induced error. Lesion characteristics that could explain variance in the PVD for each hemisphere were investigated. Taken together, these results suggest that the lesion-induced error caused by simulated lesions was not focal, but globally distributed. Previous post-processing approaches to adjust for lesions in structural analyses address the focal region where the lesion was located however, our results suggest that focal correction approaches are insufficient for the global error in morphometric measures of the injured brain.
Hydrogen Sulfide Overproduction Is Involved in Acute Ischemic Cerebral Injury Under Hyperhomocysteinemia
Authors: Ji Yan , Li Yusheng , Zhao Zichen , Li Panxing , Xie Yi
Published: November 2020

Objectives

This study aimed to identify the involvement of hydrogen sulfide overproduction in acute brain injury under ischemia/reperfusion and hyperhomocysteinemia.

Methods

In vitro and in vivo experiments were conducted to determine: the effect of sodium hydrosulfide treatment on the human neuroblastoma cell line (SH-SY5Y) under conditions of oxygen and glucose deprivation; the changes of hydrogen sulfide levels, inflammatory factors, energetic metabolism, and mitochondrial function in the brain tissue of rats under either ischemia/reperfusion alone or a combination of ischemia/reperfusion and hyperhomocysteinemia; and the potential mechanism underlying the relationship between homocysteine and these changes through the addition of the related inhibitors. Furthermore, experimental technologies, including western blot, enzyme-linked immunosorbent assay, immunofluorescence, reverse transcription polymerase chain reaction, and flow cytometry, were used.

Results

Our study found that high concentration of sodium hydrosulfide treatment aggravated the decrease in mitochondrial membrane potential, the increase in both mitochondrial permeability transition pore and translocation of cytochrome C, as well as the accumulation of reactive oxygen species in oxygen and glucose deprived SH-SY5Y cells. As a result, neurological deficit appeared in rats with ischemia/reperfusion or ischemia/reperfusion and hyperhomocysteinemia, and a higher water content and larger infarction size of cerebral tissue appeared in rats combined ischemia/reperfusion and hyperhomocysteinemia. Furthermore, alterations in hydrogen sulfide production, inflammatory factors, and mitochondria morphology and function were more evident under the combined ischemia/reperfusion and hyperhomocysteinemia. These changes were, however, alleviated by the addition of inhibitors for CBS, CSE, Hcy, H2S, and NF-κB, although at different levels. Finally, we observed a negative relationship between the blockage of: (a) the nuclear factor kappa-B pathway and the levels of cystathionine β-synthase and hydrogen sulfide; and (b) the hydrogen sulfide pathway and the levels of inflammatory factors.

Conclusion

Hydrogen sulfide overproduction and reactive inflammatory response are involved in ischemic cerebral injury under hyperhomocysteinemia. Future studies in this direction are warranted to provide a scientific base for targeted medicine development.