bluuebunny/crossref_metadata_2025 huggingface dataset:
Supercapacitor with Carbon/MoS2 Composites
Authors: Tobis Maciej , Sroka Sylwia , Frąckowiak Elżbieta
Published: May 2021

Transition metal dichalcogenides (TMDs) with a two-dimensional character are promising electrode materials for an electrochemical capacitor (EC) owing to their unique crystallographic structure, available specific surface area, and large variety of compounds. TMDs combine the capacitive and faradaic contribution in the electrochemical response. However, due to the fact that the TMDs have a strong catalytic effect of promoting hydrogen and oxygen evolution reaction (HER and OER), their usage in aqueous ECs is questioned. Our study shows a hydrothermal l-cysteine–assisted synthesis of two composites based on different carbon materials—multiwalled carbon nanotubes (NTs) and carbon black (Black Pearl-BP2000)—on which MoS2 nanolayers were deposited. The samples were subjected to physicochemical characterization such as X-ray diffraction and Raman spectroscopy which proved that the expected materials were obtained. Scanning electron microscopy coupled with electron dispersive spectroscopy (SEM/EDS) as well as transmission electron microscopy images confirmed vertical position of few-layered MoS2 structures deposited on the carbon supports. The synthetized samples were employed as electrode materials in symmetric ECs, and their electrochemical performance was evaluated and compared to their pure carbon supports. Among the composites, NTs/MoS2 demonstrated the best electrochemical metrics considering the conductivity and capacitance (150 Fg−1), whereas BP2000/MoS2 reached 110 Fg−1 at a current load of 0.2 Ag−1. The composites were also employed in a two-electrode cell equipped with an additional reference electrode to monitor the potential range of both electrodes during voltage extension. It has been shown that the active edge sites of MoS2 catalyze the hydrogen evolution, and this limits the EC operational voltage below 1 V. Additional tests with linear sweep voltammetry allowed to determine the operational working voltage for the cells with all materials. It has been proven that the MoS2/carbon composites possess limited operating voltage, that is, comparable to a pure MoS2 material.
A Mini-Review on Applications of 3D Printing for Microbial Electrochemical Technologies
Authors: Chung Tae Hyun , Dhar Bipro Ranjan
Published: May 2021

For the past two decades, many successful applications of microbial electrochemical technologies (METs), such as bioenergy generation, environmental monitoring, resource recovery, and platform chemicals production, have been demonstrated. Despite these tremendous potentials, the scaling-up and commercialization of METs are still quite challenging. Depending on target applications, common challenges may include expensive and tedious fabrication processes, prolonged start-up times, complex design requirements and their scalability for large-scale systems. Incorporating the three-dimensional printing (3DP) technologies have recently emerged as an effective and highly promising method for fabricating METs to demonstrate power generation and biosensing at the bench scale. Notably, low-cost and rapid fabrication of complex and miniaturized designs of METs was achieved, which is not feasible using the traditional methods. Utilizing 3DP showed tremendous potentials to aid the optimization of functional large-scale METs, which are essential for scaling-up purposes. Moreover, 3D-printed bioanode could provide rapid start-up in the current generation from METs without any time lags. Despite numerous review articles published on different scientific and applied aspects of METs, as per the authors’ knowledge, no published review articles explicitly highlighted the applicability and potential of 3DP for developing METs. Hence, this review targets to provide a current overview and status of 3DP applications for advancing METs and their future outlook.
COVID-DeepPredictor: Recurrent Neural Network to Predict SARS-CoV-2 and Other Pathogenic Viruses
Authors: Saha Indrajit , Ghosh Nimisha , Maity Debasree , Seal Arjit , Plewczynski Dariusz
Published: May 2021

The COVID-19 disease for Novel coronavirus (SARS-CoV-2) has turned out to be a global pandemic. The high transmission rate of this pathogenic virus demands an early prediction and proper identification for the subsequent treatment. However, polymorphic nature of this virus allows it to adapt and sustain in different kinds of environment which makes it difficult to predict. On the other hand, there are other pathogens like SARS-CoV-1, MERS-CoV, Ebola, Dengue, and Influenza as well, so that a predictor is highly required to distinguish them with the use of their genomic information. To mitigate this problem, in this work COVID-DeepPredictor is proposed on the framework of deep learning to identify an unknown sequence of these pathogens. COVID-DeepPredictor uses Long Short Term Memory as Recurrent Neural Network for the underlying prediction with an alignment-free technique. In this regard, k-mer technique is applied to create Bag-of-Descriptors (BoDs) in order to generate Bag-of-Unique-Descriptors (BoUDs) as vocabulary and subsequently embedded representation is prepared for the given virus sequences. This predictor is not only validated for the dataset using K-fold cross-validation but also for unseen test datasets of SARS-CoV-2 sequences and sequences from other viruses as well. To verify the efficacy of COVID-DeepPredictor, it has been compared with other state-of-the-art prediction techniques based on Linear Discriminant Analysis, Random Forests, and Gradient Boosting Method. COVID-DeepPredictor achieves 100% prediction accuracy on validation dataset while on test datasets, the accuracy ranges from 99.51 to 99.94%. It shows superior results over other prediction techniques as well. In addition to this, accuracy and runtime of COVID-DeepPredictor are considered simultaneously to determine the value of k in k-mer, a comparative study among k values in k-mer, Bag-of-Descriptors (BoDs), and Bag-of-Unique-Descriptors (BoUDs) and a comparison between COVID-DeepPredictor and Nucleotide BLAST have also been performed. The code, training, and test datasets used for COVID-DeepPredictor are available at http://www.nitttrkol.ac.in/indrajit/projects/COVID-DeepPredictor/.
Genome-Wide Association Study Uncover the Genetic Architecture of Salt Tolerance-Related Traits in Common Wheat (Triticum aestivum L.)
Authors: Quan Xiaoyan , Liu Jindong , Zhang Ning , Xie Chunjuan , Li Hongmei , Xia Xianchun , He Wenxing , Qin Yuxiang
Published: May 2021

Soil salinity is a serious threat to wheat yield affecting sustainable agriculture. Although salt tolerance is important for plant establishment at seedling stage, its genetic architecture remains unclear. In the present study, we have evaluated eight salt tolerance–related traits at seedling stage and identified the loci for salt tolerance by genome-wide association study (GWAS). This GWAS panel comprised 317 accessions and was genotyped with the wheat 90 K single-nucleotide polymorphism (SNP) chip. In total, 37 SNPs located at 16 unique loci were identified, and each explained 6.3 to 18.6% of the phenotypic variations. Among these, six loci were overlapped with previously reported genes or quantitative trait loci, whereas the other 10 were novel. Besides, nine loci were detected for two or more traits, indicating that the salt-tolerance genetic architecture is complex. Furthermore, five candidate genes were identified for salt tolerance–related traits, including kinase family protein, E3 ubiquitin-protein ligase-like protein, and transmembrane protein. SNPs identified in this study and the accessions with more favorable alleles could further enhance salt tolerance in wheat breeding. Our results are useful for uncovering the genetic mechanism of salt tolerance in wheat at seeding stage.
Polygenic Scores and Parental Predictors: An Adult Height Study Based on the United Kingdom Biobank and the Framingham Heart Study
Authors: You Chong , Zhou Zhenwei , Wen Jia , Li Yun , Pang Cheng Heng , Du Haoyang , Wang Ziwen , Zhou Xiao-Hua , King Daniel A. , Liu Ching-Ti , Huang Jie
Published: May 2021

Human height is a polygenic trait, influenced by a large number of genomic loci. In the pre-genomic era, height prediction was based largely on parental height. More recent predictions of human height have made great strides by integrating genotypic data from large biobanks with improved statistical techniques. Nevertheless, recent studies have not leveraged parental height, an added feature that we hypothesized would offer complementary predictive value. In this study, we assessed the predictive power of polygenic risk scores (PRS) combined with the traditional parental height predictors. Our study analyzed genotypic data and parental height from 1,071 trios from the United Kingdom Biobank and 444 trios from the Framingham Heart Study. We explored a series of statistical models to fully evaluate the performance of several PRS constructed together with parental information and proposed a model we call PRS++ that includes gender, parental height, and PRSs of parents and proband. Our estimate of height with an R2 of ∼0.82 is, to our knowledge, the most accurate estimate yet achieved for predicting human adult height. Without parental information, the R2 from the best PRS-driven model is ∼0.73. In summary, using adult height prediction as an example, we demonstrated that traditional predictors still play important roles and merit integration into the current trends of intensive PRS approaches.
MeImmS: Predict Clinical Benefit of Anti-PD-1/PD-L1 Treatments Based on DNA Methylation in Non-small Cell Lung Cancer
Authors: Shang Shipeng , Li Xin , Gao Yue , Guo Shuang , Sun Dailin , Zhou Hanxiao , Sun Yue , Wang Peng , Zhi Hui , Bai Jing , Ning Shangwei , Li Xia
Published: May 2021

Immunotherapy has become an effective therapy for cancer treatment. However, the development of biomarkers to predict immunotherapy response still remains a challenge. We have developed the DNA Methylation Immune Score, named “MeImmS,” which can predict clinical benefits of non-small cell lung cancer (NSCLC) patients based on DNA methylation of 8 CpG sites. The 8 CpG sites regulate the expression of immune-related genes and MeImmS was related to immune-associated pathways, exhausted T cell markers and immune cells. Copy-number loss in 1p36.33 may affect the response of cancer patients to immunotherapy. In addition, SAA1, CXCL10, CCR5, CCL19, CXCL11, CXCL13, and CCL5 were found to be key immune regulatory genes in immunotherapy. Together, MeImmS discovered the heterogeneous of NSCLC patients and guided the immunotherapy of cancer patients in the future.
Safranal Alleviated OVA-Induced Asthma Model and Inhibits Mast Cell Activation
Authors: Lertnimitphun Peeraphong , Zhang Wenhui , Fu Wenwei , Yang Baican , Zheng Changwu , Yuan Man , Zhou Hua , Zhang Xue , Pei Weizhong , Lu Yue , Xu Hongxi
Published: May 2021

Introduction

Asthma is a chronic and recurring airway disease, which related to mast cell activation. Many compounds derived from Chinese herbal medicine has promising effects on stabilizing mast cells and decreasing inflammatory mediator production. Safranal, one of the active compounds from Crocus sativus, shows many anti-inflammatory properties. In this study, we evaluated the effect of safranal in ovalbumin (OVA)-induced asthma model. Furthermore, we investigate the effectiveness of safranal on stabilizing mast cell and inhibiting the production of inflammatory mediators in passive systemic anaphylaxis (PSA) model.

Methods

OVA-induced asthma and PSA model were used to evaluate the effect of safranal in vivo. Lung tissues were collected for H&E, TB, IHC, and PAS staining. ELISA were used to determine level of IgE and chemokines (IL-4, IL-5, TNF-α, and IFN-γ). RNA sequencing was used to uncovers genes that safranal regulate. Bone marrow-derived mast cells (BMMCs) were used to investigate the inhibitory effect and mechanism of safranal. Cytokine production (IL-6, TNF-α, and LTC4) and NF-κB and MAPKs signaling pathway were assessed.

Results

Safranal reduced the level of serum IgE, the number of mast cells in lung tissue were decreased and Th1/Th2 cytokine levels were normalized in OVA-induced asthma model. Furthermore, safranal inhibited BMMCs degranulation and inhibited the production of LTC4, IL-6, and TNF-α. Safranal inhibits NF-κB and MAPKs pathway protein phosphorylation and decreases NF-κB p65, AP-1 nuclear translocation. In the PSA model, safranal reduced the levels of histamine and LTC4 in serum.

Conclusions

Safranal alleviates OVA-induced asthma, inhibits mast cell activation and PSA reaction. The possible mechanism occurs through the inhibition of the MAPKs and NF-κB pathways.
Physiologically Relevant Concentrations of Dolutegravir, Emtricitabine, and Efavirenz Induce Distinct Metabolic Alterations in HeLa Epithelial and BV2 Microglial Cells
Authors: George Joseph W. , Mattingly Jane E. , Roland Nashanthea J. , Small Cassandra M. , Lamberty Benjamin G. , Fox Howard S. , Stauch Kelly L.
Published: May 2021

Microglia, the resident brain phagocytes, likely play a key role in human immunodeficiency virus (HIV) infection of the central nervous system (CNS) and subsequent neuropathogenesis; however, the nature of the infection-induced changes that yield damaging CNS effects and the stimuli that provoke microglial activation remains elusive, especially in the current era of using antiretroviral (ARV) drugs for ARV therapy (ART). Altered microglial metabolism can modulate cellular functionality and pathogenicity in neurological disease. While HIV infection itself alters brain energy metabolism, the effect of ARV drugs, particularly those currently used in treatment, on metabolism is understudied. Dolutegravir (DTG) and emtricitabine (FTC) combination, together with tenofovir (TAF or TDF), is one of the recommended first line treatments for HIV. Despite the relatively good tolerability and safety profile of FTC, a nucleoside reverse transcriptase inhibitor, and DTG, an integrase inhibitor, adverse side effects have been reported and highlight a need to understand off-target effects of these medications. We hypothesized that similar to previous ART regimen drugs, DTG and FTC side effects involve mitochondrial dysfunction. To increase detection of ARV-induced mitochondrial effects, highly glycolytic HeLa epithelial cells were forced to rely on oxidative phosphorylation by substituting galactose for glucose in the growth media. We assessed ATP levels, resazurin oxidation-reduction (REDOX), and mitochondrial membrane potential following 24-hour exposure (to approximate effects of one dose equivalent) to DTG, FTC, and efavirenz (EFV, a known mitotoxic ARV drug). Further, since microglia support productive HIV infection, act as latent HIV cellular reservoirs, and when dysfunctional likely contribute to HIV-associated neurocognitive disorders, the experiments were repeated using BV2 microglial cells. In HeLa cells, FTC decreased mitochondrial REDOX activity, while DTG, similar to EFV, impaired both mitochondrial ATP generation and REDOX activity. In contrast to HeLa cells, DTG increased cellular ATP generation and mitochondrial REDOX activity in BV2 cells. Bioenergetic analysis revealed that DTG, FTC, and EFV elevated BV2 cell mitochondrial respiration. DTG and FTC exposure induced distinct mitochondrial functional changes in HeLa and BV2 cells. These findings suggest cell type-specific metabolic changes may contribute to the toxic side effects of these ARV drugs.
IL-10−/− Enhances DCs Immunity Against Chlamydia psittaci Infection via OX40L/NLRP3 and IDO/Treg Pathways
Authors: Li Qiang , Li Xiaohui , Quan Hongkun , Wang Yihui , Qu Guanggang , Shen Zhiqiang , He Cheng
Published: May 2021

Chlamydia psittaci (C. psittaci) is a common zoonotic agent that affects both poultry and humans. Interleukin 10 (IL-10) is an anti-inflammatory factor produced during chlamydial infection, while dendritic cells (DCs) are powerful antigen-presenting cells that induce a primary immune response in the host. However, IL-10 and DCs regulatory mechanisms in C. psittaci infection remain elusive. In vivo and in vitro investigations of the regulatory mechanisms were performed. IL-10−/− mice, conditional DCs depletion mice (zinc finger dendritic cell-diphtheria toxin receptor [zDC-DTR]), and double-deficient mice (DD, IL-10−/−/zDCDTR/DTR) were intranasally infected with C. psittaci. The results showed that more than 90% of IL-10−/− mice, 70% of wild-type mice, and 60% of double-deficient mice survived, whereas all zDC-DTR mice died. A higher lymphocyte proliferation index was found in the IL-10 inhibitor mice and IL-10−/− mice. Moreover, severe lesions and high bacterial loads were detected in the zDC-DTR mice compared with double-deficient mice. In vitro studies revealed increased OX40-OX40 ligand (OX40-OX40L) activation and CD4+T cell proliferation. Besides, the expression of indoleamine 2, 3-dioxygenase (IDO), and regulatory T cells were significantly reduced in the co-culture system of CD4+ T cells and IL-10−/− DCs in C. psittaci infection. Additionally, the activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome increased to facilitate the apoptosis of DCs, leading to rapid clearance of C. psittaci. Our study showed that IL-10−/− upregulated the function of deficient DCs by activating OX40-OX40L, T cells, and the NLPR3 inflammasome, and inhibiting IDO, and regulatory T cells. These effects enhanced the survival rate of mice and C. psittaci clearance. Our research highlights the mechanism of IL-10 interaction with DCs, OX40-OX40L, and the NLPR3 inflammasome, as potential targets against C. psittaci infection.
Quercetin Attenuates Trauma-Induced Heterotopic Ossification by Tuning Immune Cell Infiltration and Related Inflammatory Insult
Authors: Li Juehong , Sun Ziyang , Luo Gang , Wang Shuo , Cui Haomin , Yao Zhixiao , Xiong Hao , He Yunwei , Qian Yun , Fan Cunyi
Published: May 2021

Heterotopic ossification (HO) is one of the most intractable disorders following musculoskeletal injury and is characterized by the ectopic presence of bone tissue in the soft tissue leading to severe loss of function in the extremities. Recent studies have indicated that immune cell infiltration and inflammation are involved in aberrant bone formation. In this study, we found increased monocyte/macrophage and mast cell accumulation during early HO progression. Macrophage depletion by clodronate liposomes and mast cell stabilization by cromolyn sodium significantly impeded HO formation. Therefore, we proposed that the dietary phytochemical quercetin could also suppress immune cell recruitment and related inflammatory responses to prevent HO. As expected, quercetin inhibited the monocyte-to-macrophage transition, macrophage polarization, and mast cell activation in vitro in a dose-dependent manner. Using a murine burn/tenotomy model, we also demonstrated that quercetin attenuated inflammatory responses and HO in vivo. Furthermore, elevated SIRT1 and decreased acetylated NFκB p65 expression were responsible for the mechanism of quercetin, and the beneficial effects of quercetin were reversed by the SIRT1 antagonist EX527 and mimicked by the SIRT agonist SRT1720. The findings in this study suggest that targeting monocyte/macrophage and mast cell activities may represent an attractive approach for therapeutic intervention of HO and that quercetin may serve as a promising therapeutic candidate for the treatment of trauma-induced HO by modulating SIRT1/NFκB signaling.
Study on the Immune Escape Mechanism of Acute Myeloid Leukemia With DNMT3A Mutation
Authors: Que Yimei , Li Huimin , Lin Liman , Zhu Xiaojian , Xiao Min , Wang Ying , Zhu Li , Li Dengju
Published: May 2021

DNA (cytosine-5)-methyltransferase 3A (DNMT3A)-mutated acute myeloid leukemia (AML) has a poor prognosis, but the exact mechanism is still unclear. Here, we aimed to explore the mechanism of immune escape in AML with DNMT3A mutation. We constructed a DNMT3A knockout clone and DNMT3A-R882H-mutated clones. RNA-seq results showed that transcription factors and macrophage inflammatory proteins were significantly downregulated in the DNMT3A mutant clones. KEGG enrichment and gene set enrichment analysis (GSEA) showed that a large number of genes were enriched in inflammatory immune-related pathways, such as the toll-like receptor signaling pathway. Therefore, we co-cultured AML cells with macrophages. The DNMT3A-mutated AML cells attenuated M1 macrophage polarization and resisted its killing effect in vitro and in vivo. In xenografts, the tumor volumes in the experimental group were significantly larger than those in the control group, and the proportion of M2 macrophages was significantly higher. After the co-culture, the increase in pro-inflammatory cytokine expression in the mutant cells was significantly lower than that in the control group, while that in immunosuppressive factors was not significantly different. In co-cultivated supernatants, the concentration of inflammatory factors in the experimental group was significantly lower than that in the control group, while that of immunosuppressive factors was significantly higher. Resistin significantly promoted the expression of inflammatory proteins in AML cells. It relieved the inhibitory effect of DNMT3A mutation, promoted the phenotypic recovery of the co-cultured macrophages, eliminated resistance, and regulated the immune microenvironment. Thus, resistin may serve as an ancillary drug for patients with DNMT3A-mutated AML.
Nasal Epithelial Barrier Integrity and Tight Junctions Disruption in Allergic Rhinitis: Overview and Pathogenic Insights
Authors: Nur Husna Siti Muhamad , Tan Hern-Tze Tina , Md Shukri Norasnieda , Mohd Ashari Noor Suryani , Wong Kah Keng
Published: May 2021

Allergic rhinitis (AR) is a common disorder affecting up to 40% of the population worldwide and it usually persists throughout life. Nasal epithelial barrier constitutes the first line of defense against invasion of harmful pathogens or aeroallergens. Cell junctions comprising of tight junctions (TJs), adherens junctions, desmosomes and hemidesmosomes form the nasal epithelial barrier. Impairment of TJ molecules plays causative roles in the pathogenesis of AR. In this review, we describe and discuss the components of TJs and their disruption leading to development of AR, as well as regulation of TJs expression by epigenetic changes, neuro-immune interaction, epithelial-derived cytokines (thymic stromal lymphopoietin, IL-25 and IL-33), T helper 2 (Th2) cytokines (IL-4, IL-5, IL-6 and IL-13) and innate lymphoid cells. These growing evidence support the development of novel therapeutic approaches to restore nasal epithelial TJs expression in AR patients.
ZIKV Disrupts Placental Ultrastructure and Drug Transporter Expression in Mice
Authors: Andrade Cherley Borba Vieira , Monteiro Victoria Regina de Siqueira , Coelho Sharton Vinicius Antunes , Gomes Hanailly Ribeiro , Sousa Ronny Paiva Campos , Nascimento Veronica Muller de Oliveira , Bloise Flavia Fonseca , Matthews Stephen Giles , Bloise Enrrico , Arruda Luciana Barros , Ortiga-Carvalho Tania Maria
Published: May 2021

Congenital Zika virus (ZIKV) infection can induce fetal brain abnormalities. Here, we investigated whether maternal ZIKV infection affects placental physiology and metabolic transport potential and impacts the fetal outcome, regardless of viral presence in the fetus at term. Low (103 PFU-ZIKVPE243; low ZIKV) and high (5x107 PFU-ZIKVPE243; high ZIKV) virus titers were injected into immunocompetent (ICompetent C57BL/6) and immunocompromised (ICompromised A129) mice at gestational day (GD) 12.5 for tissue collection at GD18.5 (term). High ZIKV elicited fetal death rates of 66% and 100%, whereas low ZIKV induced fetal death rates of 0% and 60% in C57BL/6 and A129 dams, respectively. All surviving fetuses exhibited intrauterine growth restriction (IUGR) and decreased placental efficiency. High-ZIKV infection in C57BL/6 and A129 mice resulted in virus detection in maternal spleens and placenta, but only A129 fetuses presented virus RNA in the brain. Nevertheless, pregnancies in both strains produced fetuses with decreased head sizes (p<0.05). Low-ZIKV-A129 dams had higher IL-6 and CXCL1 levels (p<0.05), and their placentas showed increased CCL-2 and CXCL-1 contents (p<0.05). In contrast, low-ZIKV-C57BL/6 dams had an elevated CCL2 serum level and increased type I and II IFN expression in the placenta. Notably, less abundant microvilli and mitochondrial degeneration were evidenced in the placental labyrinth zone (Lz) of ICompromised and high-ZIKV-ICompetent mice but not in low-ZIKV-C57BL/6 mice. In addition, decreased placental expression of the drug transporters P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) and the lipid transporter Abca1 was detected in all ZIKV-infected groups, but Bcrp and Abca1 were only reduced in ICompromised and high-ZIKV ICompetent mice. Our data indicate that gestational ZIKV infection triggers specific proinflammatory responses and affects placental turnover and transporter expression in a manner dependent on virus concentration and maternal immune status. Placental damage may impair proper fetal-maternal exchange function and fetal growth/survival, likely contributing to congenital Zika syndrome.
IL-35 Regulates the Function of Immune Cells in Tumor Microenvironment
Authors: Liu Kewei , Huang Ai , Nie Jun , Tan Jun , Xing Shijie , Qu Yue , Jiang Ke
Published: May 2021

Interleukin-35 (IL-35) is a heterodimeric cytokine composed of Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35 that has recently been shown to play diverse and important roles in the tumor microenvironment (TME). Owing to its immunosuppressive activity and ability to promote tumor growth and progression, IL-35 is widely recognized as a key mediator of TME status. Immune cells are key mediators of diverse tumor-related phenotypes, and immunosuppressive cytokines such as IL-35 can promote tumor growth and metastasis in TME. These influences should be considered together. Since tumor immunotherapy based on immune checkpoint blockade remains ineffective in many patients due to tumoral resistance, a new target or efficacy enhancing factor is urgently needed. Suppressing IL-35 production and activity has been demonstrated as an effective factor that inhibits tumor cells viability, and further investigation of this cytokine is warranted. However, the mechanistic basis for IL-35-mediated regulation of immune cells in the TME remains to be fully clarified. In the present review, we explore the roles of IL-35 in regulating immune cells within the TME. In addition, we highlight IL-35 as a specific immunological target and discuss its possible relevance in the context of immunotherapy. Lastly, we sought to summarize potential future research directions that may guide the advancement of current understanding regarding the role of this important cytokine as a regulator of oncogenesis.
HLA Desensitization in Solid Organ Transplantation: Anti-CD38 to Across the Immunological Barriers
Authors: Joher Nizar , Matignon Marie , Grimbert Philippe
Published: May 2021

The presence of anti-human leucocyte antigen (HLA) antibodies in the potential solid organ transplant recipient’s blood is one of the main barriers to access to a transplantation. The HLA sensitization is associated with longer waitlist time, antibody mediated rejection and transplant lost leading to increased recipient’s morbidity and mortality. However, solid organ transplantation across the HLA immunological barriers have been reported in recipients who were highly sensitized to HLA using desensitization protocols. These desensitization regimens are focused on the reduction of circulating HLA antibodies. Despite those strategies improve rates of transplantation, it remains several limitations including persistent high rejection rate and worse long-term outcomes when compare with non-sensitized recipient population. Currently, interest is growing in the development of new desensitization approaches which, beyond targeting antibodies, would be based on the modulation of alloimmune pathways. Plasma cells appears as an interesting target given their critical role in antibody production. In the last decade, CD38-targeting immunotherapies, such as daratumumab, have been recognized as a key component in the treatment of myeloma by inducing an important plasma cell depletion. This review focuses on an emerging concept based on targeting CD38 to desensitize in the field of transplantation.
Baseline Study of Trace Element Concentrations in Sediments of the Intertidal Zone of Amazonian Oceanic Beaches
Authors: Vilhena Jéssica C. E. , Amorim Ana , Ribeiro Lourenço , Duarte Bernardo , Pombo Maíra
Published: May 2021

Analyzing the presence and quantifying trace elements is of paramount importance to understand natural environmental processes and monitor the degree of anthropogenic disturbance to mitigate impacts already caused. Here, we aimed to establish a baseline of the trace elements profile and concentrations in sandy sediments of intertidal areas of three Amazonian beaches (Brazil). For each beach, sediments were collected from three different sectors (south, center, and north) and five shoreline distance levels (from the high- to the low-water mark), totalizing 15 samples per beach. The concentration of the different trace elements (Mg, Al, P, S, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Br, Rb, Sr, Y, Zr, Cd, Sn, I, Hg, and Pb) was determined by Total reflection X-ray Fluorescence spectrometry. Sediment was also characterized for its grain size, organic matter, and pH. To assess possible enrichment due to anthropogenic activities we compared trace element levels with the values for the Earth’s crust and calculated pollution indexes: geoaccumulation index (Igeo), ecological risk index (RI), contamination factor (CF), pollution load index (PLI), and sediment quality guideline (SQG), threshold effects level (TEL) and probable effects level (PEL). Individual trace metal concentrations did not vary significantly between beaches, sectors, or sample levels, evidencing a homogeneity of trace elements composition and concentrations across this environment. Igeo indicated 62.2% of the sampling stations uncontaminated, 20.0% from uncontaminated to moderately contaminated, and 4.44% (two sampling stations) strongly contaminated, the same two areas classified as high ecological risk by RI. Most of the sampling points presented low CF. Cadmium and Hg were the only elements that showed moderate to very high values of CF. According to the SQGs, 77.7 and 8.8% of the sampling points presented values above the moderate threshold effect level (SQG-TEL) and probable effect level (SQG-PEL), respectively. All points were classified as non-polluted according to the PLI. Our results show that the three beaches present safe levels of almost of the elements demonstrating the good state of preservation. Most of the indexes classified the sampling points as non-polluted, except for Cd and Hg in a few specific sampling points.
Evolutionarily Stable Coevolution Between a Plastic Lytic Virus and Its Microbial Host
Authors: Choua Melinda , Heath Michael R. , Bonachela Juan A.
Published: May 2021

Hosts influence and are influenced by viral replication. Cell size, for example, is a fundamental trait for microbial hosts that can not only alter the probability of viral adsorption, but also constrain the host physiological processes that the virus relies on to replicate. This intrinsic connection can affect the fitness of both host and virus, and therefore their mutual evolution. Here, we study the coevolution of bacterial hosts and their viruses by considering the dependence of viral performance on the host physiological state (viral plasticity). To this end, we modified a standard host-lytic phage model to include viral plasticity, and compared the coevolutionary strategies emerging under different scenarios, including cases in which only the virus or the host evolve. For all cases, we also obtained the evolutionary prediction of the traditional version of the model, which assumes a non-plastic virus. Our results reveal that the presence of the virus leads to an increase in host size and growth rate in the long term, which benefits both interacting populations. Our results also show that viral plasticity and evolution influence the classic host quality-quantity trade-off. Poor nutrient environments lead to abundant low-quality hosts, which tends to increase viral infection time. Conversely, richer nutrient environments lead to fewer but high-quality hosts, which decrease viral infection time. Our results can contribute to advancing our understanding of the microbial response to changing environments. For instance, both cell size and viral-induced mortality are essential factors that determine the structure and dynamics of the marine microbial community, and therefore our study can improve predictions of how marine ecosystems respond to environmental change. Our study can also help devise more reliable strategies to use phage to, for example, fight bacterial infections.
Harmless or Threatening? Interpreting the Results of Molecular Diagnosis in the Context of Virus-Host Relationships
Authors: Abade dos Santos Fábio A. , Portela Sara J. , Nogueira Teresa , Carvalho Carina L. , de Sousa Rita , Duarte Margarida D.
Published: May 2021

Molecular methods, established in the 1980s, expanded and delivered tools for the detection of vestigial quantities of nucleic acids in biological samples. Nucleotide sequencing of these molecules reveals the identity of the organism it belongs to. However, the implications of such detection are often misinterpreted as pathogenic, even in the absence of corroborating clinical evidence. This is particularly significant in the field of virology where the concepts of commensalism, and other benign or neutral relationships, are still very new. In this manuscript, we review some fundamental microbiological concepts including commensalism, mutualism, pathogenicity, and infection, giving special emphasis to their application in virology, in order to clarify the difference between detection and infection. We also propose a system for the correct attribution of terminology in this context.
Molecular Events Occurring in Lipophagy and Its Regulation in Flaviviridae Infection
Authors: Wu Keke , Fan Shuangqi , Zou Linke , Zhao Feifan , Ma Shengming , Fan Jindai , Li Xiaowen , Zhao Mingqiu , Yan Huichao , Chen Jinding
Published: May 2021

Diseases caused by Flaviviridae have a wide global and economic impact due to high morbidity and mortality. Flaviviridae infection usually leads to severe, acute or chronic diseases, such as liver injury and liver cancer resulting from hepatitis C virus (HCV) infection, dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) caused by dengue virus (DENV). Given the highly complex pathogenesis of Flaviviridae infections, they are still not fully understood at present. Accumulating evidence suggests that host autophagy is disrupted to regulate the life cycle of Flaviviridae. Organelle-specific autophagy is able to selectively target different organelles for quality control, which is essential for regulating cellular homeostasis. As an important sub process of autophagy, lipophagy regulates lipid metabolism by targeting lipid droplets (LDs) and is also closely related to the infection of a variety of pathogenic microorganisms. In this review, we briefly understand the LDs interaction relationship with Flaviviridae infection, outline the molecular events of how lipophagy occurs and the related research progress on the regulatory mechanisms of lipophagy in Flaviviridae infection. Exploring the crosstalk between viral infection and lipophagy induced molecular events may provide new avenues for antiviral therapy.
Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients
Authors: Zhang Guang-Zhi , Wu Zuo-Long , Li Chun-Ying , Ren En-Hui , Yuan Wen-Hua , Deng Ya-Jun , Xie Qi-Qi
Published: May 2021

Background

Osteosarcoma is a frequent bone malignancy in children and young adults. Despite the availability of some prognostic biomarkers, most of them fail to accurately predict prognosis in osteosarcoma patients. In this study, we used bioinformatics tools and machine learning algorithms to establish an autophagy-related long non-coding RNA (lncRNA) signature to predict the prognosis of osteosarcoma patients.

Methods

We obtained expression and clinical data from osteosarcoma patients in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We acquired an autophagy gene list from the Human Autophagy Database (HADb) and identified autophagy-related lncRNAs by co-expression analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the autophagy-related lncRNAs were conducted. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of the autophagy-related lncRNA signature and validate the relationship between the signature and osteosarcoma patient survival in an independent cohort. We also investigated the relationship between the signature and immune cell infiltration.

Results

We initially identified 69 autophagy-related lncRNAs, 13 of which were significant predictors of overall survival in osteosarcoma patients. Kaplan-Meier analyses revealed that the 13 autophagy-related lncRNAs could stratify patients based on their outcomes. Receiver operating characteristic curve analyses confirmed the superior prognostic value of the lncRNA signature compared to clinically used prognostic biomarkers. Importantly, the autophagy-related lncRNA signature predicted patient prognosis independently of clinicopathological characteristics. Furthermore, we found that the expression levels of the autophagy-related lncRNA signature were significantly associated with the infiltration levels of different immune cell subsets, including T cells, NK cells, and dendritic cells.

Conclusion

The autophagy-related lncRNA signature established here is an independent and robust predictor of osteosarcoma patient survival. Our findings also suggest that the expression of these 13 autophagy-related lncRNAs may promote osteosarcoma progression by regulating immune cell infiltration in the tumor microenvironment.
Notch3-Dependent Effects on Adult Neurogenesis and Hippocampus-Dependent Learning in a Modified Transgenic Model of CADASIL
Authors: Ehret Fanny , Moreno Traspas Ricardo , Neumuth Marie-Theres , Hamann Bianca , Lasse Daniela , Kempermann Gerd
Published: May 2021

We and others have reported that Notch3 is a regulator of adult hippocampal neurogenesis. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), the most common genetic form of vascular dementia, is caused by mutations in Notch3. The present study intended to investigate whether there is a correlation between altered adult hippocampal neurogenesis and spatial memory performance in CADASIL transgenic mice. To overcome visual disabilities that hampered behavioral testing of the original mice (on an FVB background) we back-crossed the existing TgN3R169C CADASIL mouse model onto the C57BL/6J background. These animals showed an age-dependent increase in the pathognomonic granular osmiophilic material (GOM) deposition in the hippocampus. Analysis in the Morris water maze task at an age of 6 and 12 months revealed deficits in re-learning and perseverance in the CADASIL transgenic mice. Overexpression of Notch3 alone resulted in deficits in the use of spatial strategies and diminished adult neurogenesis in both age groups. The additional CADASIL mutation compensated the effect on strategy usage but not on adult neurogenesis. In brain bank tissue samples from deceased CADASIL patients we found signs of new neurons, as assessed by calretinin immunohistochemistry, but no conclusive quantification was possible. In summary, while our study confirmed the role of Notch3 in adult neurogenesis, we found a specific effect of the CADASIL mutation only on the reversion of the Notch3 effect on behavior, particularly visible at 6 months of age, consistent with a loss of function. The mutation did not revert the Notch3-dependent changes in adult neurogenesis or otherwise affected adult neurogenesis in this model.
PTEN Expression Regulates Gap Junction Connectivity in the Retina
Authors: Chen Ashley M. , Azar Shaghauyegh S. , Harris Alexander , Brecha Nicholas C. , Pérez de Sevilla Müller Luis
Published: May 2021

Manipulation of the phosphatase and tensin homolog (PTEN) pathway has been suggested as a therapeutic approach to treat or prevent vision loss due to retinal disease. In this study, we investigated the effects of deleting one copy of Pten in a well-characterized class of retinal ganglion cells called α-ganglion cells in the mouse retina. In Pten+/– retinas, α-ganglion cells did not exhibit major changes in their dendritic structure, although most cells developed a few, unusual loop-forming dendrites. By contrast, α-ganglion cells exhibited a significant decrease in heterologous and homologous gap junction mediated cell coupling with other retinal ganglion and amacrine cells. Additionally, the majority of OFF α-ganglion cells (12/18 cells) formed novel coupling to displaced amacrine cells. The number of connexin36 puncta, the predominant connexin that mediates gap junction communication at electrical synapses, was decreased by at least 50% on OFF α-ganglion cells. Reduced and incorrect gap junction connectivity of α-ganglion cells will affect their functional properties and alter visual image processing in the retina. The anomalous connectivity of retinal ganglion cells would potentially limit future therapeutic approaches involving manipulation of the Pten pathway for treating ganglion cell degeneration in diseases like glaucoma, traumatic brain injury, Parkinson’s, and Alzheimer’s diseases.
Local Accumulation of Axonal Mitochondria in the Optic Nerve Glial Lamina Precedes Myelination
Authors: Wilkison Samantha J. , Bright Cora L. , Vancini Ricardo , Song Daniel J. , Bomze Howard M. , Cartoni Romain
Published: May 2021

Mitochondria are essential for neurons and must be optimally distributed along their axon to fulfill local functions. A high density of mitochondria has been observed in retinal ganglion cell (RGC) axons of an unmyelinated region of the optic nerve, called the glial lamina (GL) in mouse (lamina cribrosa in human). In glaucoma, the world's leading cause of irreversible blindness, the GL is the epicenter of RGC degeneration and is connected to mitochondrial dysfunction. It is generally accepted that the local accumulation of mitochondria in the GL is established due to the higher energy requirement of unmyelinated axons. Here we revisit the connection between mitochondrial positioning and myelin in RGC axons. We show that the high density of mitochondria in the GL is restricted to larger axons and is established before myelination. Thus, contrary to a longstanding belief in the field, the myelination pattern is not responsible for the establishment of the local accumulation of mitochondria in GL axons. Our findings open new research avenues likely critical to understanding the pathophysiology of glaucoma.
Insect Consciousness
Authors: Overgaard Morten
Published: May 2021

The question of consciousness in other species, not least species very physically different from humans such as insects, is highly challenging for a number of reasons. One reason is that we do not have any available empirical method to answer the question. Another reason is that current theories of consciousness disagree about the relation between physical structure and consciousness, i.e., whether consciousness requires specific, say, neural structures or whether consciousness can be realized in different ways. This article sets out to analyze if and how there could be an empirical and/or a theoretical approach to the topic on the basis of current consciousness research in humans.
Sleep Disorders in Children With Autism Spectrum Disorder: Insights From Animal Models, Especially Non-human Primate Model
Authors: Feng Shufei , Huang Haoyu , Wang Na , Wei Yuanyuan , Liu Yun , Qin Dongdong
Published: May 2021

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder with deficient social skills, communication deficits and repetitive behaviors. The prevalence of ASD has increased among children in recent years. Children with ASD experience more sleep problems, and sleep appears to be essential for the survival and integrity of most living organisms, especially for typical synaptic development and brain plasticity. Many methods have been used to assess sleep problems over past decades such as sleep diaries and parent-reported questionnaires, electroencephalography, actigraphy and videosomnography. A substantial number of rodent and non-human primate models of ASD have been generated. Many of these animal models exhibited sleep disorders at an early age. The aim of this review is to examine and discuss sleep disorders in children with ASD. Toward this aim, we evaluated the prevalence, clinical characteristics, phenotypic analyses, and pathophysiological brain mechanisms of ASD. We highlight the current state of animal models for ASD and explore their implications and prospects for investigating sleep disorders associated with ASD.
Retracing Schwann Cell Developmental Transitions in Embryonic Dissociated DRG/Schwann Cell Cocultures in Mice
Authors: Sundaram Venkat Krishnan , El Jalkh Tatiana , Barakat Rasha , Fernandez Camille Julie Isabelle , Massaad Charbel , Grenier Julien
Published: May 2021

Embryonic Dissociated Dorsal Root Ganglia (DRG) cultures are often used to investigate the role of novel molecular pathways or drugs in Schwann cell development and myelination. These cultures largely recapitulate the order of cellular and molecular events that occur in Schwann cells of embryonic nerves. However, the timing of Schwann cell developmental transitions, notably the transition from Schwann Cell Precursors (SCP) to immature Schwann cells (iSC) and then to myelinating Schwann cells, has not been estimated so far in this culture system. In this study, we determined the expression profiles of Schwann cell developmental genes during the first week of culture and then compared our data to the expression profiles of these genes in developing spinal nerves. This helped in identifying that SCP transition into iSC between the 5th and 7th day in vitro. Furthermore, we also investigated the transition of immature cells into pro-myelinating and myelinating Schwann cells upon the induction of myelination in vitro. Our results suggest that Schwann cell differentiation beyond the immature stage can be observed as early as 4 days post the induction of myelination in cocultures. Finally, we compared the myelinating potential of coculture-derived Schwann cell monocultures to cultures established from neonatal sciatic nerves and found that both these culture systems exhibit similar myelinating phenotypes. In effect, our results allow for a better understanding and interpretation of coculture experiments especially in studies that aim to elucidate the role of a novel actor in Schwann cell development and myelination.