bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Pyroptosis-Related Signature for Predicting Prognosis and Indicating Immune Microenvironment Features in Osteosarcoma
Authors: Zhang Yiming , He Rong , Lei Xuan , Mao Lianghao , Jiang Pan , Ni Chenlie , Yin Zhengyu , Zhong Xinyu , Chen Chen , Zheng Qiping , Li Dapeng
Published: December 2021

Osteosarcoma is a common malignant bone tumor with a propensity for drug resistance, recurrence, and metastasis. A growing number of studies have elucidated the dual role of pyroptosis in the development of cancer, which is a gasdermin-regulated novel inflammatory programmed cell death. However, the interaction between pyroptosis and the overall survival (OS) of osteosarcoma patients is poorly understood. This study aimed to construct a prognostic model based on pyroptosis-related genes to provide new insights into the prognosis of osteosarcoma patients. We identified 46 differentially expressed pyroptosis-associated genes between osteosarcoma tissues and normal control tissues. A total of six risk genes affecting the prognosis of osteosarcoma patients were screened to form a pyroptosis-related signature by univariate and LASSO regression analysis and verified using GSE21257 as a validation cohort. Combined with other clinical characteristics, including age, gender, and metastatic status, we found that the pyroptosis-related signature score, which we named “PRS-score,” was an independent prognostic factor for patients with osteosarcoma and that a low PRS-score indicated better OS and a lower risk of metastasis. The result of ssGSEA and ESTIMATE algorithms showed that a lower PRS-score indicated higher immune scores, higher levels of tumor infiltration by immune cells, more active immune function, and lower tumor purity. In summary, we developed and validated a pyroptosis-related signature for predicting the prognosis of osteosarcoma, which may contribute to early diagnosis and immunotherapy of osteosarcoma.
Predicted Epitope Abundance Supports Vaccine-Induced Cytotoxic Protection Against SARS-CoV-2 Variants of Concern
Authors: Martín-Galiano Antonio J. , Díez-Fuertes Francisco , McConnell Michael J. , López Daniel
Published: December 2021

The effect of emerging SARS-CoV-2 variants on vaccine efficacy is of critical importance. In this study, the potential impact of mutations that facilitate escape from the cytotoxic cellular immune response in these new virus variants for the 551 most abundant HLA class I alleles was analyzed. Computational prediction showed that most of these alleles, that cover >90% of the population, contain enough epitopes without escape mutations in the principal SARS-CoV-2 variants. These data suggest that the cytotoxic cellular immune protection elicited by vaccination is not greatly affected by emerging SARS-CoV-2 variants.
The Immune Barrier of Porcine Uterine Mucosa Differs Dramatically at Proliferative and Secretory Phases and Could Be Positively Modulated by Colonizing Microbiota
Authors: Han Deping , Sun Peng , Hu Yanxin , Wang Jing , Hua Guoying , Chen Jianfei , Shao Chuyun , Tian Fan , Darwish Hesham Y. A. , Tai Yurong , Yang Xue , Chang Jianyu , Ma Yunfei
Published: December 2021

Endometrial immune response is highly associated with the homeostatic balance of the uterus and embryo development; however, the underlying molecular regulatory mechanisms are not fully elucidated. Herein, the porcine endometrium showed significant variation in mucosal immunity in proliferative and secretory phases by single-cell RNA sequencing. The loose arrangement and high motility of the uterine epithelium in the proliferative phase gave opportunities for epithelial cells and dendritic cells to cross talk with colonizing microbial community, guiding lymphocyte migration into the mucosal and glandular epithelium. The migrating lymphocytes were primarily NK and CD8+ T cells, which were robustly modulated by the chemokine signaling. In the secretory phase, the significantly strengthened mechanical mucosal barrier and increased immunoglobulin A alleviated the migration of lymphocytes into the epithelium when the neuro-modulation, mineral uptake, and amino acid metabolism were strongly upregulated. The noticeably increased intraepithelial lymphocytes were positively modulated by the bacteria in the uterine cavity. Our findings illustrated that significant mucosal immunity variation in the endometrium in the proliferative and secretory phases was closely related to intraepithelial lymphocyte migration, which could be modulated by the colonizing bacteria after cross talk with epithelial cells with higher expressions of chemokine.
Conditional Deletion of Pdcd1 Identifies the Cell-Intrinsic Action of PD-1 on Functional CD8 T Cell Subsets for Antitumor Efficacy
Authors: Raghavan Sukanya , Tovbis-Shifrin Nataliya , Kochel Christina , Sawant Anandi , Mello Marielle , Sathe Manjiri , Blumenschein Wendy , Muise Eric S. , Chackerian Alissa , Pinheiro Elaine M. , Rosahl Thomas W. , Luche Hervé , de Waal Malefyt Rene
Published: December 2021

Programmed cell death-1 (PD-1) blockade has a profound effect on the ability of the immune system to eliminate tumors, but many questions remain about the cell types involved and the underlying mechanisms of immune activation. To shed some light on this, the cellular and molecular events following inhibition of PD-1 signaling was investigated in the MC-38 colon carcinoma model using constitutive (PD-1 KO) and conditional (PD1cKO) mice and in wild-type mice treated with PD-1 antibody. The impact on both tumor growth and the development of tumor immunity was assessed. In the PD-1cKO mice, a complete deletion of Pdcd1 in tumor-infiltrating T cells (TILs) after tamoxifen treatment led to the inhibition of tumor growth of both small and large tumors. Extensive immune phenotypic analysis of the TILs by flow and mass cytometry identified 20-different T cell subsets of which specifically 5-CD8 positive ones expanded in all three models after PD-1 blockade. All five subsets expressed granzyme B and interferon gamma (IFNγ). Gene expression analysis of the tumor further supported the phenotypic analysis in both PD-1cKO- and PD-1 Ab-treated mice and showed an upregulation of pathways related to CD4 and CD8 T-cell activation, enhanced signaling through costimulatory molecules and IFNγ, and non-T-cell processes. Altogether, using PD-1cKO mice, we define the intrinsic nature of PD-1 suppression of CD8 T-cell responses in tumor immunity.
Potential Immune Biomarker Candidates and Immune Subtypes of Lung Adenocarcinoma for Developing mRNA Vaccines
Authors: Wang Yang , Tan Huaicheng , Yu Ting , Chen Xiaoxuan , Jing Fangqi , Shi Huashan
Published: December 2021

mRNA vaccines against cancer have advantages in safety, improved therapeutic efficacy, and large-scale production. Therefore, our purpose is to identify immune biomarkers and to analyze immune status for developing mRNA vaccines and selecting appropriate patients for vaccination. We downloaded clinical information and RNA-seq data of 494 LUAD patients from TCGA. LUAD mutational information was hierarchically clustered by NMF package (Version 0.23.0). DeconstructSigs package (Version 1.8.0) and NMF consistency clustering were used to identify mutation signatures. Maftools package (Version 2.6.05) was used to select LUAD-related immune biomarkers. TIMER was used to discuss the correlation between genetic mutations and cellular components. Unsupervised clustering Pam method was used to identify LUAD immune subtypes. Log-rank test and univariate/multivariate cox regression were used to predict the prognosis of immune subtypes. Dimensionality reduction analysis was dedicated to the description of LUAD immune landscape. LUAD patients are classified into four signatures: T >C, APOBEC mutation, age, and tobacco. Then, GPRIN1, MYRF, PLXNB2, SLC9A4, TRIM29, UBA6, and XDH are potential LUAD-related immune biomarker candidates to activate the immune response. Next, we clustered five LUAD-related immune subtypes (IS1–IS5) by prognostic prediction. IS3 showed prolonged survival. The reliability of our five immune subtypes was validated by Thorsson’s results. IS2 and IS4 patients had high tumor mutation burden and large number of somatic mutations. Besides, we identified that immune subtypes of cold immunity (patients with IS2 and IS4) are ideal mRNA vaccination recipients. Finally, LUAD immune landscape revealed immune cells and prognostic conditions, which provides important information to select patients for vaccination. GPRIN1, MYRF, PLXNB2, SLC9A4, TRIM29, UBA6, and XDH are potential LUAD-related immune biomarker candidates to activate the immune response. Patients with IS2 and IS4 might potentially be immunization-sensitive patients for vaccination.
Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea
Authors: Zhang Huaxiong , Zhang Yiya , Li Yangfan , Wang Yaling , Yan Sha , Xu San , Deng Zhili , Yang Xinling , Xie Hongfu , Li Ji
Published: December 2021

Rosacea is significantly associated with dementia, particularly Alzheimer’s disease (AD). However, the common underlying molecular mechanism connecting these two diseases remains limited. This study aimed to reveal the common molecular regulatory networks and identify the potential therapeutic drugs for rosacea and AD. There were 747 overlapped DEGs (ol-DEGs) that were detected in AD and rosacea, enriched in inflammation-, metabolism-, and apoptosis-related pathways. Using the TF regulatory network analysis, 37 common TFs and target genes were identified as hub genes. They were used to predict the therapeutic drugs for rosacea and AD using the DGIdb/CMap database. Among the 113 predicted drugs, melatonin (MLT) was co-associated with both RORA and IFN-γ in AD and rosacea. Subsequently, network pharmacology analysis identified 19 pharmacological targets of MLT and demonstrated that MLT could help in treating AD/rosacea partly by modulating inflammatory and vascular signaling pathways. Finally, we verified the therapeutic role and mechanism of MLT on rosacea in vivo and in vitro. We found that MLT treatment significantly improved rosacea-like skin lesion by reducing keratinocyte-mediated inflammatory cytokine secretion and repressing the migration of HUVEC cells. In conclusion, this study contributes to common pathologies shared by rosacea and AD and identified MLT as an effective treatment strategy for rosacea and AD via regulating inflammation and angiogenesis.
Safety of African Swine Fever Vaccine Candidate Lv17/WB/Rie1 in Wild Boar: Overdose and Repeated Doses
Authors: Barasona Jose A. , Cadenas-Fernández Estefanía , Kosowska Aleksandra , Barroso-Arévalo Sandra , Rivera Belén , Sánchez Rocío , Porras Néstor , Gallardo Carmina , Sánchez-Vizcaíno Jose M.
Published: December 2021

African swine fever (ASF) is a highly lethal infectious disease that affects domestic pigs and wild boar. Outbreaks of ASF have grown considerably in the last decade causing important economic consequences for the swine industry. Its control is hampered by the lack of an effective treatment or vaccine. In Europe, the wild boar is a key wild reservoir for ASF. The results of the oral vaccination trial of wild boar with Lv17/WB/Rie1 are hope for this problem. However, this vaccine candidate has certain safety concerns, since it is a naturally attenuated vaccine. Therefore, the current study aims to evaluate the safety of this vaccine candidate in terms of overdose (high dose) and repeated doses (revaccination) in wild boar. Low-dose orally vaccinated animals developed only a slight transient fever after vaccination and revaccination. This was also the case for most of the high-dose vaccinated wild boar, except for one of them which succumbed after revaccination. Although this fatality was related to hierarchical fights between animals, we consider that further studies are required for clarification. Considering these new results and the current epidemiological situation of ASF in wild boar, this vaccine prototype is a promising tool for the control of the disease in these wild populations, although further studies are needed.
Type III Interferons: Emerging Roles in Autoimmunity
Authors: Manivasagam Sindhu , Klein Robyn S.
Published: December 2021

Type III interferons (IFNs) or the lambda IFNs (IFNLs or IFN-λs) are antimicrobial cytokines that play key roles in immune host defense at endothelial and epithelial barriers. IFNLs signal via their heterodimeric receptor, comprised of two subunits, IFNLR1 and interleukin (IL)10Rβ, which defines the cellular specificity of the responses to the cytokines. Recent studies show that IFNL signaling regulates CD4+ T cell differentiation, favoring Th1 cells, which has led to the identification of IFNL as a putative therapeutic target for autoimmune diseases. Here, we summarize the IFNL signaling pathways during antimicrobial immunity, IFNL-mediated immunomodulation of both innate and adaptive immune cells, and induction of autoimmunity.
Inhibition of PI3Kδ Differentially Regulates Poly I:C– and Human Metapneumovirus–Induced PD–L1 and PD–L2 Expression in Human Bronchial Epithelial Cells
Authors: Ogawa Tomohiro , Kan-o Keiko , Shiota Ayaka , Fujita Akitaka , Ishii Yumiko , Fukuyama Satoru , Matsumoto Koichiro
Published: December 2021

Bronchial epithelial cells are front sentinels eliciting innate and adaptive immunity to respiratory viral pathogens. Recognition of viral double-stranded RNA induces antiviral interferon (IFN) responses in bronchial epithelial cells. Co-inhibitory molecules programmed cell death 1 ligand 1 (PD-L1) and ligand 2 (PD-L2) were also induced on bronchial epithelial cells, which bind programmed cell death 1 on T cell and inhibit the function of virus-specific cytotoxic T lymphocyte. A previous study showed that antiviral type I IFN increased PD-L1 and PD-L2 expression in cultured melanoma cells. However, it remains unknown whether antiviral IFNs affect PD-L1 and PD-L2 expression in bronchial epithelial cells. In addition, we previously reported that inhibition of PI3Kδ signaling enhanced antiviral IFN responses in human primary bronchial epithelial cells (PBECs). Here we assessed the effect of exogenous IFNs or a selective PI3Kδ inhibitor IC87114 on PD-L1 and PD-L2 in PBECs stimulated with a synthetic double-stranded RNA poly I:C or human metapneumovirus. Treatment with IFNβ or IFNλ increased PD-L1 and PD-L2, and IFNβ or IFNλ treatment plus poly I:C further increased both expressions. Treatment with IC87114 or transfection with siRNA targeting PI3K p110δ enhanced poly I:C–induced gene and protein expression of PD-L2, whereas IC87114 suppressed poly I:C–induced PD-L1. IC87114 enhanced poly I:C–induced gene expression of IFNβ, IFNλ, and IFN-regulated genes via increased TBK1 and IRF3 phosphorylation. Transfection with siIRF3 counteracted the enhancement of poly I:C–induced PD-L2 by IC87114, whereas IC87114 suppressed poly I:C–induced PD-L1 regardless of transfection with siNC or siIRF3. Similar effects of IC87114 on PD-L1 and PD-L2 expression were observed in human metapneumovirus–infected PBECs. We showed for the first time that type I and type III IFNs induced the expression of PD-L1 and PD-L2 in PBECs. Our findings suggest that during viral infections, inhibition of PI3Kδ differentially regulates PD-L1 and PD-L2 expression in bronchial epithelial cells.
Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
Authors: Zhang Wen , Wang Yao , Li Chuanwei , Xu Yu , Wang Xia , Wu Di , Gao Zhan , Qian Hang , You Zaichun , Zhang Zhiren , He Binfeng , Wang Guansong
Published: December 2021

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a condition with an imbalanced inflammatory response and delayed resolution of inflammation. Macrophage polarization plays an important role in inflammation and resolution. However, the mechanism of macrophage polarization in ALI/ARDS is not fully understood. We found that mice with lipopolysaccharide administration developed lung injury with the accumulation of extracellular cold-inducible RNA-binding protein (eCIRP) in the lungs. eCIRP, as a damage-associated molecular pattern (DAMP), inhibited M2 macrophage polarization, thereby tipping the balance toward inflammation rather than resolution. Anti-CIRP antibodies reversed such phenotypes. The levels of macrophage erythropoietin (EPO) receptor (EPOR) were reduced after eCIRP treatment. Myeloid-specific EPOR-deficient mice displayed restrained M2 macrophage polarization and impaired inflammation resolution. Mechanistically, eCIRP impaired Rab26, a member of Ras superfamilies of small G proteins, and reduced the transportation of surface EPOR, which resulted in macrophage polarization toward the M1 phenotype. Moreover, EPO treatment hardly promotes M2 polarization in Rab26 knockout (KO) macrophages through EPOR. Collectively, macrophage EPOR signaling is impaired by eCIRP through Rab26 during ALI/ARDS, leading to the restrained M2 macrophage polarization and delayed inflammation resolution. These findings identify a mechanism of persistent inflammation and a potential therapy during ALI/ARDS.
Gamma-Irradiated Fowl Cholera Mucosal Vaccine: Potential Vaccine Candidate for Safe and Effective Immunization of Chicken Against Fowl Cholera
Authors: Dessalegn Bereket , Bitew Molalegne , Asfaw Destaw , Khojaly Esraa , Ibrahim Saddam Mohammed , Abayneh Takele , Gelaye Esayas , Unger Hermann , Wijewardana Viskam
Published: December 2021

Fowl cholera (FC) caused by Pasteurella multocida is among the serious infectious diseases of poultry. Currently, formalin inactivated FC (FI-FC) vaccine is widely used in Ethiopia. However, reports of the disease complaint remain higher despite the use of the vaccine. The aim of this study was to develop and evaluate gamma-irradiated mucosal FC vaccines that can be used nationally. In a vaccination-challenge experiment, the performance of gamma-irradiated P. multocida (at 1 kGy) formulated with Montanide gel/01 PR adjuvant was evaluated at different dose rates (0.5 and 0.3 ml) and routes (intranasal, intraocular, and oral), in comparison with FI-FC vaccine in chicken. Chickens received three doses of the candidate vaccine at 3-week intervals. Sera, and trachea and crop lavage were collected to assess the antibody levels using indirect and sandwich ELISAs, respectively. Challenge exposure was conducted by inoculation at 3.5×109 CFU/ml of P. multocida biotype A intranasally 2 weeks after the last immunization. Repeated measures ANOVA test and Kaplan Meier curve analysis were used to examine for statistical significance of antibody titers and survival analysis, respectively. Sera IgG and secretory IgA titers were significantly raised after second immunization (p=0.0001). Chicken survival analysis showed that intranasal and intraocular administration of the candidate vaccine at the dose of 0.3 ml resulted in 100% protection as compared to intramuscular injection of FI-FC vaccine, which conferred 85% protection (p=0.002). In conclusion, the results of this study showed that gamma-irradiated FC mucosal vaccine is safe and protective, indicating its potential use for immunization of chicken against FC.
Targeting Innate Immunity in Breast Cancer Therapy: A Narrative Review
Authors: Ye Yanqi , Xu Chun , Chen Fengqian , Liu Qi , Cheng Ning
Published: December 2021

Although breast cancer has been previously considered “cold” tumors, numerous studies are currently conducted to explore the great potentials of immunotherapies in improving breast cancer patient outcomes. In addition to the focus on stimulating adaptive immunity for antitumor responses, growing evidence showed the importance of triggering host innate immunity to eradicate established tumors and/or control tumor metastasis of breast cancer. In this review, we first briefly introduce the breast tumor immune microenvironment. We also discuss innate immune targets and pathways and mechanisms of their synergy with the adaptive antitumor response and other treatment strategies. Lastly, we review clinical trials targeting innate immune pathways for breast cancer therapies.
Comparison of Two Diagnostic Assays for Anti-Laminin 332 Mucous Membrane Pemphigoid
Authors: Goletz Stephanie , Giurdanella Federica , Holtsche Maike M. , Nijenhuis Miranda , Horvath Barbara , Diercks Gilles F. H. , Zillikens Detlef , Hashimoto Takashi , Schmidt Enno , Pas Hendri H.
Published: December 2021

Anti-laminin 332 mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by predominant mucosal lesions and autoantibodies against laminin 332. The exact diagnosis of anti-laminin 332 MMP is important since nearly 30% of patients develop solid cancers. This study compared two independently developed diagnostic indirect immunofluorescence (IF) tests based on recombinant laminin 332 expressed in HEK239 cells (biochip mosaic assay) and the migration trails of cultured keratinocytes rich in laminin 332 (footprint assay). The sera of 54 anti-laminin 332 MMP, 35 non-anti-laminin 332 MMP, and 30 pemphigus vulgaris patients as well as 20 healthy blood donors were analyzed blindly and independently. Fifty-two of 54 and 54/54 anti-laminin 332 MMP sera were positive in the biochip mosaic and the footprint assay, respectively. In the 35 non-anti-laminin 332 MMP sera, 3 were positive in both tests and 4 others showed weak reactivity in the footprint assay. In conclusion, both assays are easy to perform, highly sensitive, and specific, which will further facilitate the diagnosis of anti-laminin 332 MMP.
Epidermis as a Platform for Bacterial Transmission
Authors: Baquero Fernando , Saralegui Claudia , Marcos-Mencía Daniel , Ballestero Luna , Vañó-Galván Sergio , Moreno-Arrones Óscar M. , del Campo Rosa
Published: December 2021

The epidermis constitutes a continuous external layer covering the body, offering protection against bacteria, the most abundant living organisms that come into contact with this barrier. The epidermis is heavily colonized by commensal bacterial organisms that help protect against pathogenic bacteria. The highly regulated and dynamic interaction between the epidermis and commensals involves the host’s production of nutritional factors promoting bacterial growth together to chemical and immunological bacterial inhibitors. Signal trafficking ensures the system’s homeostasis; conditions that favor colonization by pathogens frequently foster commensal growth, thereby increasing the bacterial population size and inducing the skin’s antibacterial response, eliminating the pathogens and re-establishing the normal density of commensals. The microecological conditions of the epidermis favors Gram-positive organisms and are unsuitable for long-term Gram-negative colonization. However, the epidermis acts as the most important host-to-host transmission platform for bacteria, including those that colonize human mucous membranes. Bacteria are frequently shared by relatives, partners, and coworkers. The epidermal bacterial transmission platform of healthcare workers and visitors can contaminate hospitalized patients, eventually contributing to cross-infections. Epidermal transmission occurs mostly via the hands and particularly through fingers. The three-dimensional physical structure of the epidermis, particularly the fingertips, which have frictional ridges, multiplies the possibilities for bacterial adhesion and release. Research into the biology of bacterial transmission via the hands is still in its infancy; however, tribology, the science of interacting surfaces in relative motion, including friction, wear and lubrication, will certainly be an important part of it. Experiments on finger-to-finger transmission of microorganisms have shown significant interindividual differences in the ability to transmit microorganisms, presumably due to genetics, age, sex, and the gland density, which determines the physical, chemical, adhesive, nutritional, and immunological status of the epidermal surface. These studies are needed to optimize interventions and strategies for preventing the hand transmission of microorganisms.
m6A Regulator-Mediated Methylation Modification Patterns and Characteristics of Immunity in Blood Leukocytes of COVID-19 Patients
Authors: Qiu Xiangmin , Hua Xiaoliang , Li Qianyin , Zhou Qin , Chen Juan
Published: December 2021

Both RNA N6-methyladenosine (m6A) modification of SARS-CoV-2 and immune characteristics of the human body have been reported to play an important role in COVID-19, but how the m6A methylation modification of leukocytes responds to the virus infection remains unknown. Based on the RNA-seq of 126 samples from the GEO database, we disclosed that there is a remarkably higher m6A modification level of blood leukocytes in patients with COVID-19 compared to patients without COVID-19, and this difference was related to CD4+ T cells. Two clusters were identified by unsupervised clustering, m6A cluster A characterized by T cell activation had a higher prognosis than m6A cluster B. Elevated metabolism level, blockage of the immune checkpoint, and lower level of m6A score were observed in m6A cluster B. A protective model was constructed based on nine selected genes and it exhibited an excellent predictive value in COVID-19. Further analysis revealed that the protective score was positively correlated to HFD45 and ventilator-free days, while negatively correlated to SOFA score, APACHE-II score, and crp. Our works systematically depicted a complicated correlation between m6A methylation modification and host lymphocytes in patients infected with SARS-CoV-2 and provided a well-performing model to predict the patients’ outcomes.
Antibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity
Authors: Kurtovic Liriye , Drew Damien R. , Dent Arlene E. , Kazura James W. , Beeson James G.
Published: December 2021

ThePlasmodium falciparumcircumsporozoite protein (CSP) forms the basis of leading subunit malaria vaccine candidates. However, the mechanisms and specific targets of immunity are poorly defined. Recent findings suggest that antibody-mediated complement-fixation and activation play an important role in immunity. Here, we investigated the regions of CSP targeted by functional complement-fixing antibodies and the antibody properties associated with this activity. We quantified IgG, IgM, and functional complement-fixing antibody responses to different regions of CSP among Kenyan adults naturally exposed to malaria (n=102) and using a series of rabbit vaccination studies. Individuals who acquired functional complement-fixing antibodies had higher IgG, IgM and IgG1 and IgG3 to CSP. Acquired complement-fixing antibodies targeted the N-terminal, central-repeat, and C-terminal regions of CSP, and positive responders had greater antibody breadth compared to those who were negative for complement-fixing antibodies (p<0.05). Using rabbit vaccinations as a model, we confirmed that IgG specific to the central-repeat and non-repeat regions of CSP could effectively fix complement. However, vaccination with near full length CSP in rabbits poorly induced antibodies to the N-terminal region compared to naturally-acquired immunity in humans. Poor induction of N-terminal antibodies was also observed in a vaccination study performed in mice. IgG and IgM to all three regions of CSP play a role in mediating complement-fixation, which has important implications for malaria vaccine development.
Methodological Appraisal of Literature Concerning the Analysis of Genetic Variants or Protein Levels of Complement Components on Susceptibility to Infection by Trypanosomatids: A Systematic Review
Authors: Tirado Thais Cristina , Moura Larine Lowry , Shigunov Patrícia , Figueiredo Fabiano Borges
Published: December 2021

Background

Trypanosomatids are protozoa responsible for a wide range of diseases, with emphasis on Chagas Disease (CD) and Leishmaniasis, which are in the list of most relevant Neglected Tropical Diseases (NTD) according to World Health Organization (WHO). During the infectious process, immune system is immediately activated, and parasites can invade nucleated cells through a broad diversity of receptors. The complement system − through classical, alternative and lectin pathways − plays a role in the first line of defense against these pathogens, acting in opsonization, phagocytosis and lysis of parasites. Genetic modifications in complement genes, such as Single Nucleotide Polymorphisms (SNPs), can influence host susceptibility to these parasites and modulate protein expression.

Methods

In March and April 2021, a literature search was conducted at the PubMed and Google Scholar databases and the reference lists obtained were verified. After applying the inclusion and exclusion criteria, the selected studies were evaluated and scored according to eleven established criteria regarding their thematic approach and design, aiming at the good quality of publications.

Results

Twelve papers were included in this systematic review: seven investigating CD and five focusing on Leishmaniasis. Most articles presented gene and protein approaches, careful determination of experimental groups, and adequate choice of experimental techniques, although several of them were not up-to-date. Ten studies explored the association of polymorphisms and haplotypes with disease progression, with emphasis on lectin complement pathway genes. Decreased and increased patient serum protein levels were associated with susceptibility to CD and Visceral Leishmaniasis, respectively.

Conclusion

This systematic review shows the influence of genetic alterations in complement genes on the progression of several infectious diseases, with a focus on conditions caused by trypanosomatids, and contributes suggestions and evidence to improve experimental design in future research proposals.
Chloroplast Ultrastructure and Photosynthetic Response of the Dinoflagellate Akashiwo sanguinea Throughout Infection by Amoebophrya sp.
Authors: Chen Tiantian , Liu Yun , Hu Zhangxi , Song Shuqun , Li Caiwen
Published: December 2021

The endoparasitic dinoflagellate Amoebophrya infects a number of marine dinoflagellates, including toxic and harmful algal bloom-forming species. The parasite kills its host and has been proposed to be a determining factor in the demise of dinoflagellate blooms in restricted coastal waters. Previous studies have mainly focused on the occurrence, prevalence, and diversity of Amoebophrya, while the interactions between the parasite and its host have received limited attention. Herein, an Amoebophrya sp.-Akashiwo sanguinea co-culture was established from Chinese coastal waters, and morphological, physiological, and transcriptional changes throughout an infection cycle of the parasite were systemically studied. The parasitic dinoflagellate was very infectious, resulting in an infection rate up to 85.83% at a dinospore:host ratio of 10:1. Infected host cells died eventually and released approximately 370 dinospores/cell. The host nuclear structures were rapidly degraded by Amoebophrya infection, and the chloroplasts of parasitized host cells remained intact until the parasite filled the almost entire cell structure. Nevertheless, infected cultures showed sustained but lower levels of photosynthetic performance (∼64% of control cultures), and the photosynthesis-related genes were significantly down-regulated. These findings provide a better understanding of the biological basis of the complex parasite-host interactions, which will be helpful to further elucidate the ecological significance of parasitic dinoflagellates in marine ecosystems.
Sedimentary Organic Matter Shapes Macrofaunal Communities but Not Benthic Nutrient Fluxes in Contrasting Habitats Along the Northwest Atlantic Continental Margin
Authors: Miatta Marta , Snelgrove Paul V. R.
Published: December 2021

The heterogeneous topography of continental margins can influence patterns of resource availability and biodiversity in deep-sea sediments, potentially altering ecosystem functioning (e.g., organic matter remineralization). Noting a lack of studies that address the latter, we contrasted spatial patterns and drivers of benthic nutrient fluxes and multiple characteristics of macrofaunal communities in shelf, slope, canyon and inter-canyon sedimentary habitats along the Northwest Atlantic continental margin. Replicate sediment push cores were collected from 10 stations (229–996 m depth), incubated for ∼48 h to estimate fluxes of nitrate, nitrite, ammonium, phosphate, and silicate (as a measure of organic matter remineralization) and subsequently analyzed to characterize macrofaunal communities. We also considered various environmental factors, including sedimentary organic matter quantity and quality, and assessed their influence on fluxes and macrofauna. Comparatively high macrofaunal density and distinct community composition and trait expression characterized Georges Canyon, where elevated sedimentary organic matter suggested important lateral transport mechanisms along this canyon axis, with deposition of organic matter strongly affecting biological communities but not benthic nutrient fluxes. Lower penetration of macrofauna into the sediments, distinct community composition, biological traits, and higher nutrient flux rates characterized inter-canyon habitats compared to slope habitats at similar depths. Within inter-canyons, intermediate to low organic matter suggested hydrodynamic forces inhibiting organic matter deposition, affecting biological and functional processes. The input of fresh phytodetritus to the seafloor was the best predictor of macrofaunal density and diversity and contributed to variation in macrofaunal community composition and biological trait expression, together with latitude, depth, and other measures of organic matter quantity and quality. Benthic nutrient fluxes revealed complex variation, with disproportionate effects of few key macrofaunal taxa, together with bottom water oxygen concentration, and sediment granulometry. Our results suggest a relationship between resource availability and macrofaunal density, diversity, and taxonomic and trait composition, whereas organic matter remineralization exhibited a more complex response, which we suggest reflected variation in hydrodynamics and/or physical disturbance in heterogeneous continental margin habitats.
Dissolved Oxygen in Heterogeneous Environments Dictates the Metabolic Rate and Thermal Sensitivity of a Tropical Aquatic Crab
Authors: Fusi Marco , Daffonchio Daniele , Booth Jenny , Giomi Folco
Published: December 2021

Oxygen availability, together with water temperature, greatly varies in coastal habitats, especially in those characterized by elevated primary production. In this study, we investigate the combined role of dissolved oxygen and temperature on the thermal physiological response of the mud crab Thalamita crenata living in an equatorial system of coastal habitats. We sampled temperature, oxygen and salinity in T. crenata habitats, mangrove creeks and fringes and seagrass meadows, at Gazi Bay (Kenya). We found that seagrass meadows exhibited higher temperature and oxygen saturation than the mangrove habitats during the day, creating conditions of oxygen supersaturation. By investigating the effect of different levels of oxygen saturation on the thermal response of T. crenata, we demonstrated that the respiratory physiology of this ectotherm has a pronounced resistance to heat, directly influenced by the amount of dissolved oxygen in the water. Under low oxygen saturation levels, the mud crab significantly reduced its metabolism, becoming temperature-independent. This result shows that aquatic species can modulate their thermal response in a stringent dependency with water oxygen saturation, corroborating previous findings on the thermal response of T. crenata under supersaturation. This contribution provides further support for the need to adopt an ecologically-relevant approach to forecast the effect of climate change on marine ectothermal species.
Turnover Time of the East Sea (Sea of Japan) Meridional Overturning Circulation
Authors: Han MyeongHee , Chang Yeon S. , Kang Hyoun-Woo , Kang Dong-Jin , Kim Yong Sun
Published: December 2021

The East Sea (ES; Sea of Japan) meridional overturning circulation (MOC) serves as a crucial mechanism for the transportation of dissolved, colloidal, and suspended particulate matters, including pollutants, on the surface to deep waters via thermohaline circulation. Therefore, understanding the structure of the ES MOC is critical for characterizing its temporal and spatial distribution. Numerous studies have estimated these parameters indirectly using chemical tracers, severely limiting the accuracy of the results. In this study, we provide a method for directly estimating the turnover times of the ES MOC using the stream functions calculated from HYbrid Coordinate Ocean Model (HYCOM) reanalysis data by averaging the flow pattern in the meridional 2-D plane. Because the flow pattern is not consistent but various over time, three cases of stream function fields were computed over a 20-year period. The turnover time was estimated by calculating the time required for water particles to circulate along the streamlines. In the cases of multiple (two or three) convection cells, we considered all possible scenarios of the exchange of water particles between adjacent cells, so that they circulated over those cells until finally returning to the original position and completing the journey on the ES MOC. Three different cell cases were tested, and each case had different water particle exchange scenarios. The resulting turnover times were 17.91–58.59 years, 26.41–37.28 years, and 8.68–45.44 years for the mean, deep, and shallow convection cases, respectively. The maximum turnover time, namely 58.59 years, was obtained when circulating the water particle over all three cells, and it was approximately half of that estimated by the chemical tracers in previous studies (∼100 years). This underestimation arose because the streamlines and water particle movement were not calculated in the shallow (<300 m) and deep areas (>3,000 m) in this study. Regardless, the results of this study provide insight into the ES MOC dynamics and indicate that the traditional chemical turnover time represents only one of the various turnover scenarios that could exist in the ES.
Evaluation of Methanotroph (Methylococcus capsulatus, Bath) Bacteria Meal (FeedKind®) as an Alternative Protein Source for Juvenile Black Sea Bream, Acanthopagrus schlegelii
Authors: Xu Bingying , Liu Yuechong , Chen Kai , Wang Lei , Sagada Gladstone , Tegomo Arnaud Fabrice , Yang Yifei , Sun Yuxiao , Zheng Lu , Ullah Sami , Shao Qingjun
Published: December 2021

Single-cell proteins are attracting growing attention as viable alternatives for fishmeal (FM) in aquatic feed. Methanotroph (Methylococcus capsulatus, Bath) bacteria meal FeedKind® (FK) is a type of single cell protein with high protein content (75.14%) and desirable amino acids profile, produced by Methylococcus capsulatus (Bath) living on methane consumption. The present study evaluated the potential of replacing FM with FK in the diet of black sea bream (Acanthopagrus schlegelii). Five iso-energetic and iso-nitrogenous diets were designed with FK replacing 0, 4.13, 8.27, 16.53, and 24.80% FM protein in the basal diet (40% FM content), respectively. All the diets were fed to three replicates of fish (initial weight 6.56 ± 0.02 g) for 70 days. After the feeding trial, replacing dietary 8.27% FM protein with FK significantly improved the weight gain and specific growth rate of fish (P < 0.05), while other groups showed no significant difference in the growth performance (P > 0.05). The fish fed diets with 8.27 and 16.53% replacement levels exhibited significantly increased feeding rates. The 8.27% FK diet significantly increased the whole-body and muscle crude protein contents, apparent digestibility of crude lipid, foregut, and midgut amylase activities. The microvillus density in the midgut of fish fed the 24.80% FK diet significantly increased. The diet with 8.27% FK increased the serum triglyceride content of the fish, while the 24.80% FK diet reduced the serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol contents of the fish. In conclusion, the results indicated that replacing dietary FM protein with up to 24.80% FK had no adverse effects on the growth of black sea bream, whilst replacing 8.27% FM protein with FK enhanced its growth performance and feed utilization.
Impacts of Baobab (Adansonia digitata) Powder on the Poly(Butylene Succinate) Polymer Degradability to Form an Eco-Friendly Filler-Based Composite
Authors: Tadda Musa Abubakar , Gouda Mostafa , Lin Xiaochang , Shitu Abubakar , Abdullahi Hamza Sulayman , Zhu Songming , Li Xiaoli , Liu Dezhao
Published: December 2021

Poly (butylene succinate) (PBS) is one of the most common biodegradable plastic polymers that has recently been used in the green environmental field. Enhancement of physicochemical characteristics of these polymers by using plant-based materials like Baobab (Adansonia digitata) will improve its industrial application. This study evaluated Baobab (Adansonia digitata) powder (BP) and PBS composites under various ratios (PBS/BP: 90/10, 80/20, 70/30, 60/40, and 50/50 wt%) for their thermo-mechanical and other physicochemical properties for the industrial application. The nanoscale morphological and elemental characterization were also measured by scanning electron microscope-dispersive X-ray spectroscopy (SEM-EDS). The results revealed that PBS/BP blends of 90/10 and 50/50 showed a significantly reduced melting temperature (Tm) up to 94°C (p < 0.05) compared to PBS (114°C). Also, the dynamic viscosity, storage modulus, and loss modulus showed a significant decrease with increasing the ratio of BP in PBS/BP composite, which confirmed faster degradation than the pure PBS. In conclusion, the novel PBS/BP biomaterial is recommended for use as a carbon source for denitrification processes, as an eco-friendly faster degradable natural filler-based polymer. Besides, they could be use in food packaging and biomedical industries.
Investigating the Effects of Chemical Mechanism on Soot Formation Under High-Pressure Fuel Pyrolysis
Authors: Killingsworth Nick J. , Nguyen Tuan M. , Brown Carter , Kukkadapu Goutham , Manin Julien
Published: December 2021

We performed Computational Fluid Dynamics (CFD) simulations using a Reynolds-Averaged Navier-Stokes (RANS) turbulence model of high-pressure spray pyrolysis with a detailed chemical kinetic mechanism encompassing pyrolysis of n-dodecane and formation of polycyclic aromatic hydrocarbons. We compare the results using the detailed mechanism and those found using several different reduced chemical mechanisms to experiments carried out in an optically accessible, high-pressure, constant-volume combustion chamber. Three different soot models implemented in the CONVERGE CFD software are used: an empirical soot model, a method of moments, and a discrete sectional method. There is a large variation in the prediction of the soot between different combinations of chemical mechanisms and soot model. Furthermore, the amount of soot produced from all models is substantially less than experimental measurements. All of this indicates that there is still substantial work that needs to be done to arrive at simulations that can be relied on to accurately predict soot formation.
Albumin in Tears Modulates Bacterial Susceptibility to Topical Antibiotics in Ophthalmology
Authors: Sebbag Lionel , Broadbent Victoria L. , Kenne Danielle E. , Perrin Ashtyn L. , Mochel Jonathan P.
Published: December 2021

Bacterial keratitis is a serious and vision-threatening condition in veterinary and human patients, one that often requires culture and susceptibility testing to adjust therapy and improve clinical outcomes. The present study challenges the antimicrobial susceptibility testing (AST) paradigm in ophthalmology, enabling more accurate in vitro-to-in vivo translation by incorporating factors normally present during host-pathogen interactions in clinical patients. Thirty bacteria (10 Staphylococcus pseudintermedius, 10 Streptococcus canis, 10 Pseudomonas aeruginosa) were isolated from canine patients with infectious keratitis. For each isolate, commercial plates (Sensititre™ JOEYE2) were used to assess the minimal inhibitory concentration (MIC) of 17 different antibiotics in the absence (0% albumin, control) or presence of canine albumin (0.01–2%). For Staphylococcus pseudintermedius, the experiment was repeated with actual tear fluid collected from canine eyes with ocular surface inflammation. Kruskal-Wallis, Wilcoxon signed rank test and Spearman's correlation tests were used for statistical analysis. Clinical outcomes were unfavorable in selected canine patients with bacterial keratitis (e.g., globe perforation, graft dehiscence) despite standard AST (i.e., 0% albumin in test medium) confirming that most corneal infections (93%) were susceptible to ≥1 topical antibiotics used at the initial visit. Albumin levels ≥0.05% increased MICs in a dose-dependent, bacteria-specific, and antibiotic-specific manner. No significant differences (P = 1.000) were noted in MICs of any antibiotic whether albumin or tear fluid was added to the Mueller-Hinton broth. Percent protein binding inherent to each antibiotic was associated with clinical interpretations (Spearman's rho = −0.53, P = 0.034) but not changes in MICs. Albumin in tears impacted the efficacy of selected ophthalmic antibiotics as only the unbound portion of an antibiotic is microbiologically active. The present findings could improve decision making of clinicians managing bacterial keratitis, reduce development of antimicrobial resistance, influence current guidelines set by the Clinical and Laboratory Standards Institute, and serve as a reference for bacteriological evaluations across medical fields and across species.
Electroencephalogram Signatures of Agitation Induced by Sevoflurane and Its Association With Genetic Polymorphisms
Authors: Zhao Shuai , Han Linlin , Zhou Ruihui , Huang Shiqian , Wang Yafeng , Xu Feng , Shu Shaofang , Xia Leiming , Chen Xiangdong
Published: December 2021

Background: Volatile anesthetic-induced agitation, also called paradoxical excitation, is not uncommon during anesthesia induction. Clinically, patients with agitation may lead to self-injury or disrupt the operative position, increasing the incidence of perioperative adverse events. The study was designed to investigate clinical features of sevoflurane-induced agitation and examined whether any gene polymorphisms can potentially be used to predict agitation.

Methods: One hundred seventy-six patients underwent anesthesia induction with sevoflurane were included in this study. Frontal electroencephalogram (EEG), electromyography (EMG), and hemodynamics were recorded continuously during anesthesia induction. DNA samples were genotyped using the Illumina Infinium Asian Screening Array and the SNaPshot technology. Genetic association was analyzed by genome-wide association study. Logistic regression analysis was used to determine the role of variables in the prediction of agitation.

Results: Twenty-five (14.2%) patients experienced agitation. The depth of anesthesia index (Ai index) (p < 0.001), EMG (p < 0.001), heart rate (HR) (p < 0.001), and mean arterial pressure (MAP) (p < 0.001) rapidly increased during the agitation. EEG exhibited a shift toward high frequencies with spikes during agitation. The fast waves (alpha and beta) were more pronounced and the slow rhythms (delta) were less prominent during the occurrence of agitation. Moreover, three SNPs in the methionine synthase reductase (MTRR) gene were correlated to the susceptibility to agitation (p < 5.0 × 10−6). Carrying rs1801394 A > G (odds ratio 3.50, 95% CI 1.43–9.45) and/or rs2307116 G > A (3.31, 1.36–8.95) predicted a higher risk of agitation.

Discussion: This study suggests that the agitation/paradoxical excitation induced by sevoflurane is characterized as increases in Ai index, EMG, HR and MAP, and the high frequency with spikes in EEG. Moreover, our results provide preliminary evidence for MTRR genetic polymorphisms, involving folate metabolism function, may be related to the susceptibility to agitation.

Clinical Trial Number and Registry URL: ChiCTR1900026218; http://www.chictr.org.cn/showproj.aspx?proj=40655.