bluuebunny/crossref_metadata_2025 huggingface dataset:
CircCDYL Acts as a Tumor Suppressor in Wilms’ Tumor by Targeting miR-145-5p
Authors: Zhou Rui , Jia Wei , Gao Xiaofeng , Deng Fuming , Fu Kai , Zhao Tianxin , Li Zhongmin , Fu Wen , Liu Guochang
Published: August 2021

Circular RNAs (circRNA) have been reported to exert evident functions in many human carcinomas. However, the possible mechanisms concerning the circRNA in various tumors are still elusive. In this research, we analyzed the expression profile and biological functions of circular RNA CDYL (circCDYL, circBase ID: hsa_circ_0008285) in Wilms’ tumor. Here, miRNA and gene expression were examined by real-time PCR in Wilms’ tumor tissues and cell lines. The functions of circCDYL and its potential targets to influence cell proliferation, migration, and invasion in Wilms’ tumor cells were determined by biological functional experiments in vitro and in vivo. We predicted and analyzed potential miRNA targets through online bioinformatic tools. To validate the interactions between circCDYL and its targets, we performed RNA fluorescence in situ hybridization, biotin-coupled miRNA capture assay, and biotin-coupled probe pull-down assay. Tight junction protein l (TJP1) was proved to be the target gene of the predicted miRNA by dual-luciferase reporter assay. The expression level of TJP1 in Wilms’ tumor cells was identified via Western blot. We showed that circCDYL was downregulated in WT tissue compared with adjacent non-tumor tissue. Upregulation of circCDYL could reduce cell proliferation, migration, and invasion. Mechanically, circCDYL, functioning as a miRNA sponge, decreased the expression level of miR-145-5p and TJP1 3′UTR was validated as the target of miR-145-5p, facilitating the circCDYL/miR-145-5p/TJP1 axis. In conclusion, our study suggested circCDYL as a novel biomarker and therapeutic target for WT treatment.
TMEA, a Polyphenol in Sanguisorba officinalis, Promotes Thrombocytopoiesis by Upregulating PI3K/Akt Signaling
Authors: Li Hong , Jiang Xueqin , Shen Xin , Sun Yueshan , Jiang Nan , Zeng Jing , Lin Jing , Yue Liang , Lai Jia , Li Yan , Wu Anguo , Wang Long , Qin Dalian , Huang Feihong , Mei Qibing , Yang Jing , Wu Jianming
Published: August 2021

Thrombocytopenia is closely linked with hemorrhagic diseases, for which induction of thrombopoiesis shows promise as an effective treatment. Polyphenols widely exist in plants and manifest antioxidation and antitumour activities. In this study, we investigated the thrombopoietic effect and mechanism of 3,3′,4′-trimethylellagic acid (TMEA, a polyphenol in Sanguisorba officinalis L.) using in silico prediction and experimental validation. A KEGG analysis indicated that PI3K/Akt signalling functioned as a crucial pathway. Furthermore, the virtual molecular docking results showed high-affinity binding (a docking score of 6.65) between TMEA and mTOR, suggesting that TMEA might target the mTOR protein to modulate signalling activity. After isolation of TMEA, in vitro and in vivo validation revealed that this compound could promote megakaryocyte differentiation/maturation and platelet formation. In addition, it enhanced the phosphorylation of PI3K, Akt, mTOR, and P70S6K and increased the expression of GATA-1 and NF-E2, which confirmed the mechanism prediction. In conclusion, our findings are the first to demonstrate that TMEA may provide a novel therapeutic strategy that relies on the PI3K/Akt/mTOR pathway to facilitate megakaryocyte differentiation and platelet production.
Deficiency of Intellectual Disability-Related Gene Brpf1 Attenuated Hippocampal Excitatory Synaptic Transmission and Impaired Spatial Learning and Memory Ability
Authors: Xian Weiwei , Cao Jingli , Yuan Xiangshan , Wang Guoxiang , Jin Qiuyan , Zhang Hang , Zhou Guomin , You Linya
Published: August 2021

Patients with monoallelic bromodomain and PHD finger-containing protein 1 (BRPF1) mutations showed intellectual disability. The hippocampus has essential roles in learning and memory. Our previous work indicated that Brpf1 was specifically and strongly expressed in the hippocampus from the perinatal period to adulthood. We hypothesized that mouse Brpf1 plays critical roles in the morphology and function of hippocampal neurons, and its deficiency leads to learning and memory deficits. To test this, we performed immunofluorescence, whole-cell patch clamp, and mRNA-Seq on shBrpf1-infected primary cultured hippocampal neurons to study the effect of Brpf1 knockdown on neuronal morphology, electrophysiological characteristics, and gene regulation. In addition, we performed stereotactic injection into adult mouse hippocampus to knock down Brpf1 in vivo and examined the learning and memory ability by Morris water maze. We found that mild knockdown of Brpf1 reduced mEPSC frequency of cultured hippocampal neurons, before any significant changes of dendritic morphology showed. We also found that Brpf1 mild knockdown in the hippocampus showed a decreasing trend on the spatial learning and memory ability of mice. Finally, mRNA-Seq analyses showed that genes related to learning, memory, and synaptic transmission (such as C1ql1, Gpr17, Htr1d, Glra1, Cxcl10, and Grin2a) were dysregulated upon Brpf1 knockdown. Our results showed that Brpf1 mild knockdown attenuated hippocampal excitatory synaptic transmission and reduced spatial learning and memory ability, which helps explain the symptoms of patients with BRPF1 mutations.
Understanding the Role of Endothelial Glycocalyx in Mechanotransduction via Computational Simulation: A Mini Review
Authors: Jiang Xi Zhuo , Luo Kai H. , Ventikos Yiannis
Published: August 2021

Endothelial glycocalyx (EG) is a forest-like structure, covering the lumen side of blood vessel walls. EG is exposed to the mechanical forces of blood flow, mainly shear, and closely associated with vascular regulation, health, diseases, and therapies. One hallmark function of the EG is mechanotransduction, which means the EG senses the mechanical signals from the blood flow and then transmits the signals into the cells. Using numerical modelling methods orin silicoexperiments to investigate EG-related topics has gained increasing momentum in recent years, thanks to tremendous progress in supercomputing. Numerical modelling and simulation allows certain very specific or even extreme conditions to be fulfilled, which provides new insights and complements experimental observations. This mini review examines the application of numerical methods in EG-related studies, focusing on how computer simulation contributes to the understanding of EG as a mechanotransducer. The numerical methods covered in this review include macroscopic (i.e., continuum-based), mesoscopic [e.g., lattice Boltzmann method (LBM) and dissipative particle dynamics (DPD)] and microscopic [e.g., molecular dynamics (MD) and Monte Carlo (MC) methods]. Accounting for the emerging trends in artificial intelligence and the advent of exascale computing, the future of numerical simulation for EG-related problems is also contemplated.
Aspulvinones Suppress Postprandial Hyperglycemia as Potent α-Glucosidase Inhibitors From Aspergillus terreus ASM-1
Authors: Wu Changjing , Cui Xiang , Sun Luzhen , Lu Jiajia , Li Feng , Song Minghui , Zhang Yunxia , Hao Xinqi , Tian Congkui , Song Maoping , Liu Xiaomeng
Published: August 2021

Chemical investigation of Aspergillus terreus ASM-1 fermentation resulted in the isolation of three new prenylated aspulvinones V–X (1–3), together with the previously reported analogs, aspulvinone H (4), J-CR (5), and R (6). Their structures were elucidated by various spectroscopic methods including HRESIMS and NMR, and the absolute configurations of 2 and 3 were determined by ECD comparison. Compounds 1–6 were evaluated for α-glucosidase inhibitory effects with acarbose as positive control. As a result, compounds 1 and 4 exhibited potent α-glucosidase inhibitory activities with IC50 values of 2.2 and 4.6 µM in mixed-type manners. The thermodynamic constants recognized the interaction between inhibitors and α-glucosidase was hydrophobic force-driven spontaneous exothermic reaction. The CD spectra also indicate that the compounds 1 and 4 changed the enzyme conformation. Furthermore, compound 4 significantly suppressed the increases in postprandial blood glucose levels in the C57BL/6J mice.
Novel Imaging and Genetic Risk Markers in Takotsubo Syndrome
Authors: Arcari Luca , Limite Luca Rosario , Adduci Carmen , Sclafani Matteo , Tini Giacomo , Palano Francesca , Cosentino Pietro , Cristiano Ernesto , Cacciotti Luca , Russo Domitilla , Rubattu Speranza , Volpe Massimo , Autore Camillo , Musumeci Maria Beatrice , Francia Pietro
Published: August 2021

Takotsubo syndrome (TTS) is an increasingly recognized condition burdened by significant acute and long-term adverse events. The availability of novel techniques expanded the knowledge on TTS and allowed a more accurate risk-stratification, potentially guiding clinical management. The present review aims to summarize the recent advances in TTS prognostic evaluation with a specific focus on novel imaging and genetic markers. Parametric deformation analysis by speckle-tracking echocardiography, as well as tissue characterization by cardiac magnetic resonance imaging T1 and T2 mapping techniques, currently appear the most clinically valuable applications. Notwithstanding, computed tomography and nuclear imaging studies provided limited but promising data. A genetic predisposition to TTS has been hypothesized, though available evidence is still not sufficient. Although a genetic predisposition appears likely, further studies are needed to fully characterize the genetic background of TTS, in order to identify genetic markers that could assist in predicting disease recurrences and help in familial screening.
Machine Learning-Based Extraction of Breast Cancer Receptor Status From Bilingual Free-Text Pathology Reports
Authors: Pironet Antoine , Poirel Hélène A. , Tambuyzer Tim , De Schutter Harlinde , van Walle Lien , Mattheijssens Joris , Henau Kris , Van Eycken Liesbet , Van Damme Nancy
Published: August 2021

As part of its core business of gathering population-based information on new cancer diagnoses, the Belgian Cancer Registry receives free-text pathology reports, describing results of (pre-)malignant specimens. These reports are provided by 82 laboratories and written in 2 national languages, Dutch or French. For breast cancer, the reports characterize the status of estrogen receptor, progesterone receptor, and Erb-b2 receptor tyrosine kinase 2. These biomarkers are related with tumor growth and prognosis and are essential to define therapeutic management. The availability of population-scale information about their status in breast cancer patients can therefore be considered crucial to enrich real-world scientific studies and to guide public health policies regarding personalized medicine. The main objective of this study is to expand the data available at the Belgian Cancer Registry by automatically extracting the status of these biomarkers from the pathology reports. Various types of numeric features are computed from over 1,300 manually annotated reports linked to breast tumors diagnosed in 2014. A range of popular machine learning classifiers, such as support vector machines, random forests and logistic regressions, are trained on this data and compared using their F1 scores on a separate validation set. On a held-out test set, the best performing classifiers achieve F1 scores ranging from 0.89 to 0.92 for the four classification tasks. The extraction is thus reliable and allows to significantly increase the availability of this valuable information on breast cancer receptor status at a population level.
Geochemical Features of the Thermal and Mineral Waters From the Apuseni Mountains (Romania)
Authors: Nicula Alin-Marius , Ionescu Artur , Pop Ioan-Cristian , Roba Carmen , Forray Ferenc L. , Orăşeanu Iancu , Baciu Călin
Published: August 2021

The Apuseni Mountains are located between the large geothermal area of the Pannonian Basin and the low thermal flux Transylvanian Basin. Thermal and mineral waters have been sampled from 42 points along a NW-SE transect. The general chemistry and the water isotope (deuterium and oxygen-18) composition were analyzed. Most of the thermal aquifers are located in carbonate reservoirs. The waters mainly belong to the Ca-HCO3 hydrochemical type, excepting the western side, towards the Pannonian Basin, where the Na-HCO3 type may occur. The isotope composition indicates aquifer recharge from precipitation. The geochemical characteristics and the structural position of the study area suggest two distinct geothermal contexts. The Southern Apuseni area geothermal features are likely connected to the Neogene—Early Quaternary magmatic activity from the Mureş Valley and Zarand Depression. The geothermal manifestations in the north-western part of the study area, at the border between the Northern Apuseni and the Pannonian Depression, share features of the latter one.
Physiochemical Characteristics, Provenance, and Dynamics of Sand Dunes in the Arid Hexi Corridor
Authors: Zhu Bing-Qi , Zhang Jia-Xing , Sun Chun
Published: August 2021

Dynamic changes of aeolian landforms under changing environments in a middle-latitude desert belt is a typical problem of climate change and related landscape response. It need a comprehensive understanding of the formation mechanisms of dune landforms with the supply of material suitable for aeolian transport and favorable conditions of sediment availability and wind regimes in the region. Based on comprehensive evidences from geomorphological, sedimentological, geochemical, and hydrological analysis, this study discussed the dynamical changes of different dune landforms during the past half century and their provenance in the Hexi Corridor, China. The results show that there are two states of sand dunes movement in the Hexi Corridor in the past half century, dynamic migration and basically stable. The crescent-shaped dunes move the fastest, followed by the chains of barchan dunes. Only the top of the pyramid dunes wigwags, while the parabolic dunes and the longitudinal dunes hardly move forward. The moving speed of sand dunes is positively correlated with the wind speed ≥5 m/s at a yearly scale. The grain size of sand dunes in the western Hexi Corridor is coarser than that in the central-eastern part, and also larger than those in other deserts of northern China and of the world. Different motion modes of saltation, suspension, and creeping are identified between aeolian, alluvial/fluvial and gobi sediments. Dune sands are mainly “sediments ofin-siturising” that originated from alluvial/fluvial/lacustrine deposits of ancient rivers, lakes, and aeolian deposits in the erosion zone of the forelands of the Qilian and Beishan Mountains and the north-neighboring deserts. This reveals a significance interaction between wind and water dynamics in the formation and evolution of aeolian landforms in the arid study area. Sufficient transport capacity is evidenced for both the western and eastern parts of the Hexi Corridor, sufficient sand supply and sand availability, however, is the favorable factor for dune formation in the east part but is the limiting factor for the west.
Alteration of Gut Microbiota Relates to Metabolic Disorders in Primary Aldosteronism Patients
Authors: Liu Yu , Jiang Qingyao , Liu Zhihong , Shen Sikui , Ai Jianzhong , Zhu Yuchun , Zhou Liang
Published: August 2021

Purpose

This study aimed to determine the relationships among gut microbiota, primary aldosteronism (PA), and related metabolic disorders.

Methods

The study enrolled 13 PA patients, 26 sex-matched primary hypertension patients, and 26 sex-matched healthy controls. Demographic and clinical characteristics such as age, body mass index (BMI), blood aldosterone–renin ratio, blood potassium, blood glucose, blood lipid parameters, and history of diabetes mellitus (DM) were compared between the three groups. The gut microbiota of each participant was examined by 16S rRNA gene sequencing. Spearman correlation analysis was performed to demonstrate the relationship between gut microbiota and clinical characteristics.

Results

BMI and the percentage of DM in PA patients were higher than those in healthy controls (p < 0.05), but not higher than those in primary hypertension patients (p > 0.05). The gut microbiota of healthy controls and primary hypertension patients had a higher alpha diversity level than that of PA patients. PA patients had fewer short-chain fatty acid (SCFA)-producing genera (Prevotella, Blautia, Coprococcus, Anaerostipes, and Ruminococcus) and more inflammation-associated genera (Megamonas, Sutterella, and Streptococcus) than healthy controls (p < 0.05). The gut microbiota of PA patients was more inclined to encode microbial pathways involved in sugar metabolism, such as starch and sucrose metabolism and fructose and mannose metabolism. Blood potassium was negatively correlated with the relative abundance of Romboutsia (R = −0.364, q = 0.023). Diastolic blood pressure (DBP) was positively correlated with Romboutsia (R = 0.386, q = 0.015). Systolic blood pressure (SBP) was negatively correlated with Blautia (R = −0.349, q = 0.030).

Conclusions

The alteration of gut microbiota in PA patients, especially bacteria and pathways involved in inflammation, SCFAs, and sugar metabolism, may be associated with chronic metabolic disorders.
Production of Biodiesel From Croton gratissimus Oil Using Sulfated Zirconia and KOH as Catalysts
Authors: Jiyane Phiwe Charles , Tumba Kaniki , Musonge Paul
Published: August 2021

Optimization studies for the esterification and transesterification of oil extracted from Croton gratissimus grains were carried out using the response surface methodology (RMS) that utilizes the central composite design (CCD) and the analysis of variance (ANOVA). A 23 full-factorial rotatable CCD for three independent variables at five levels was developed in each case, giving a total of 20 experiments needed per study. The three design factors chosen for study were the catalyst concentration, methanol-to-oil ratio, and the reaction temperature. The values of the acid value of oil (in esterification) and the percentage FAME yield and FAME purity (in transesterification) were taken as the responses of the designed experiments. In the optimization of the esterification and transesterification processes, the ANOVA showed that both quadratic regression models developed were significant. The optimum operating conditions for the esterification process that could give an optimum acid value of 2.693 mg KOH/g of oil were found to be 10.96 mass% SO42–/ZrO2 catalyst concentration, 27.60 methanol-to-oil ratio, and 64°C reaction temperature. In the optimization of the transesterification process, the model revealed that the catalyst concentration and the methanol-to-oil ratio were the terms that had the most influence on the % FAME yield and the % FAME purity of the final biodiesel product. From the combined regression model, it was established that optimum responses of the 84.51% FAME yield and 90.66% FAME purity could be achieved when operating the transesterification process at 1.439 mass% KOH catalyst concentration, 7.472 methanol-to-oil ratio, and at a temperature of 63.50°C. Furthermore, in the two-step biodiesel synthesis, a predominantly monoclinic-phased sulfated zirconia (SO42–/ZrO2) catalyst exhibited high activity in the esterification of high free fatty acid oil extracted from Croton gratissimus grains. A 91% reduction in the acid value of the Croton gratissimus oil from 21.46 mg KOH/g of oil to 2.006 mg KOH/g of oil, well below the 4 mg KOH/g of oil maximum limit, was achieved. This resulted in the high FAME yield and purity of the biodiesel produced in the subsequent catalytic transesterification of oil using KOH.
Optimal Sizing of a Grid Independent Renewable Heating System for Building Decarbonisation
Authors: Chen Si , Friedrich Daniel , Yu Zhibin
Published: August 2021

As the use of fossil fuels has led to global climate change due to global warming, most countries are aiming to reduce greenhouse gas emissions through the application of renewable energies. Due to the distributed and seasonal heating demand, the decarbonisation of heating is more challenging, especially for countries that are cold in winters. Electrically powered heat pumps are considered as an attractive solution for decarbonising heating sector. Since grid-powered heat pumps may significantly increase the power demand of the grid, this paper considers using local renewable energy to provide power for heat pumps, which is known as the grid independent renewable heating system including photovoltaic, wind turbine, battery storage system and thermal energy storage. This paper investigates a complete renewable heating system (RHS) framework and sizing the components to decarbonise building heating. The relationship between the reduction of gas consumption and the requirement of battery storage system (BSS) under the corresponding installation capacity of renewable components is analysed with their technical requirements. Then, according to different investment plans, this paper uses the particle swarm optimisation algorithm for optimal sizing of each component in the RHS to find a solution to minimise CO2 emissions. The results verify that the RHS with optimal sizing can minimise CO2 emissions and reduce the operational cost of natural gas. This work provides a feasible solution of how to invest the RHS to replace the existing heating system based on gas boilers and CHPs.
Development and Validation of a Forensic Multiplex System With 38 X-InDel Loci
Authors: Chen Ling , Pan Xiyong , Wang Yuan , Du Weian , Wu Weibin , Tang Zhenya , Xiao Cheng , Han Xiaolong , Liu Chao , Liu Changhui
Published: August 2021

In the present study, a novel multiplex system, AGCU X-InDel 38 kit, was designed to amplify 38 X-InDel markers and amelogenin in a single Polymerase Chain Reaction (PCR). To demonstrate the suitability and efficiency for forensic applications, a series of validation experiments were conducted, including sensitivity, species specificity, reproducibility, stability, case samples, balance of peak height, size precision, as well as allele frequency and forensic parameter analysis. The results showed that AGCU X-InDel 38 kit was capable to get full profiles even with 62.5 pg of template DNA, and full profiles can be obtained when hematin concentration ≤25 μmol/L, or hemoglobin concentration ≤50 μmol/L, showing good tolerance to six common inhibitors. Moreover, the analyzed case samples indicated that AGCU X-InDel 38 kit had better performance for degraded and trace DNA samples. The 200 unrelated males from Guangdong Han population showed that the combined PDMale and PDFemale were both more than 0.999999999, and the combined MECKrüger, MECKishida, and MECDesmarais  Duo were 0.999369481, 0.999999917, and 0.999941556, respectively. Robust discrimination capability of this novel multiplex system could be demonstrated through the high values of forensic parameters. In conclusion, AGCU X-InDel 38 kit is sensitive, precise, reproducible, and highly informative and could be used as a complementary tool for complex and challenging kinship cases.
Human Surfactant Protein SP-A1 and SP-A2 Variants Differentially Affect the Alveolar Microenvironment, Surfactant Structure, Regulation and Function of the Alveolar Macrophage, and Animal and Human Survival Under Various Conditions
Authors: Floros Joanna , Thorenoor Nithyananda , Tsotakos Nikolaos , Phelps David S.
Published: August 2021

The human innate host defense molecules, SP-A1 and SP-A2 variants, differentially affect survival after infection in mice and in lung transplant patients. SP-A interacts with the sentinel innate immune cell in the alveolus, the alveolar macrophage (AM), and modulates its function and regulation. SP-A also plays a role in pulmonary surfactant-related aspects, including surfactant structure and reorganization. For most (if not all) pulmonary diseases there is a dysregulation of host defense and inflammatory processes and/or surfactant dysfunction or deficiency. Because SP-A plays a role in both of these general processes where one or both may become aberrant in pulmonary disease, SP-A stands to be an important molecule in health and disease. In humans (unlike in rodents) SP-A is encoded by two genes (SFTPA1 and SFTPA2) and each has been identified with extensive genetic and epigenetic complexity. In this review, we focus on functional, structural, and regulatory differences between the two SP-A gene-specific products, SP-A1 and SP-A2, and among their corresponding variants. We discuss the differential impact of these variants on the surfactant structure, the alveolar microenvironment, the regulation of epithelial type II miRNome, the regulation and function of the AM, the overall survival of the organism after infection, and others. Although there have been a number of reviews on SP-A, this is the first review that provides such a comprehensive account of the differences between human SP-A1 and SP-A2.
Haplotype-Specific Expression Analysis of MHC Class II Genes in Healthy Individuals and Rheumatoid Arthritis Patients
Authors: Houtman Miranda , Hesselberg Espen , Rönnblom Lars , Klareskog Lars , Malmström Vivianne , Padyukov Leonid
Published: August 2021

HLA-DRB1 alleles have been associated with several autoimmune diseases. For anti-citrullinated protein antibody positive rheumatoid arthritis (RA), HLA-DRB1 shared epitope (SE) alleles are the major genetic risk factors. In order to study the genetic regulation of major histocompatibility complex (MHC) Class II gene expression in immune cells, we investigated transcriptomic profiles of a variety of immune cells from healthy individuals carrying different HLA-DRB1 alleles. Sequencing libraries from peripheral blood mononuclear cells, CD4+ T cells, CD8+ T cells, and CD14+ monocytes of 32 genetically pre-selected healthy female individuals were generated, sequenced and reads were aligned to the standard reference. For the MHC region, reads were mapped to available MHC reference haplotypes and AltHapAlignR was used to estimate gene expression. Using this method, HLA-DRB and HLA-DQ were found to be differentially expressed in different immune cells of healthy individuals as well as in whole blood samples of RA patients carrying HLA-DRB1 SE-positive versus SE-negative alleles. In contrast, no genes outside the MHC region were differentially expressed between individuals carrying HLA-DRB1 SE-positive and SE-negative alleles, thus HLA-DRB1 SE alleles have a strong cis effect on gene expression. Altogether, our findings suggest that immune effects associated with different allelic forms of HLA-DR and HLA-DQ may be associated not only with differences in the structure of these proteins, but also with differences in their expression levels.
Group 2 Innate Lymphoid Cells Exhibit Tissue-Specific Dynamic Behaviour During Type 2 Immune Responses
Authors: Lok Laurence S. C. , Walker Jennifer A. , Jolin Helen E. , Scanlon Seth T. , Ishii Masaru , Fallon Padraic G. , McKenzie Andrew N. J. , Clatworthy Menna R.
Published: August 2021

Group 2 innate lymphoid cells (ILC2s) are early effectors of mucosal type 2 immunity, producing cytokines such as interleukin (IL)-13 to mediate responses to helminth infection and allergen-induced inflammation. ILC2s are also present in lymph nodes (LNs) and can express molecules required for antigen presentation, but to date there are limited data on their dynamic behaviour. We used a CD2/IL-13 dual fluorescent reporter mouse for in vivo imaging of ILC2s and Th2 T cells in real time following a type 2 priming helminth infection or egg injection. After helminth challenge, we found that ILC2s were the main source of IL-13 in lymphoid organs (Peyer’s patches and peripheral LNs), and were located in T cell areas. Intravital imaging demonstrated an increase in IL-13+ ILC2 size and movement following helminth infection, but reduced duration of interactions with T cells compared with those in homeostasis. In contrast, in the intestinal mucosa, we observed an increase in ILC2-T cell interactions post-infection, including some of prolonged duration, as well as increased IL-13+ ILC2 movement. These data suggest that ILC2 activation enhances cell motility, with the potential to increase the area of distribution of cytokines to optimise the early generation of type 2 responses. The prolonged ILC2 interactions with T cells within the intestinal mucosa are consistent with the conclusion that contact-based T cell activation may occur within inflamed tissues rather than lymphoid organs. Our findings have important implications for our understanding of the in vivo biology of ILC2s and the way in which these cells facilitate adaptive immune responses.
High Endothelial Venules: A Vascular Perspective on Tertiary Lymphoid Structures in Cancer
Authors: Vella Gerlanda , Guelfi Sophie , Bergers Gabriele
Published: August 2021

High endothelial venules (HEVs) are specialized postcapillary venules composed of cuboidal blood endothelial cells that express high levels of sulfated sialomucins to bind L-Selectin/CD62L on lymphocytes, thereby facilitating their transmigration from the blood into the lymph nodes (LN) and other secondary lymphoid organs (SLO). HEVs have also been identified in human and murine tumors in predominantly CD3+T cell-enriched areas with fewer CD20+B-cell aggregates that are reminiscent of tertiary lymphoid-like structures (TLS). While HEV/TLS areas in human tumors are predominantly associated with increased survival, tumoral HEVs (TU-HEV) in mice have shown to foster lymphocyte-enriched immune centers and boost an immune response combined with different immunotherapies. Here, we discuss the current insight into TU-HEV formation, function, and regulation in tumors and elaborate on the functional implication, opportunities, and challenges of TU-HEV formation for cancer immunotherapy.
Long-Term Temporal and Spatial Distribution of Coliform Bacteria in Jiaozhou Bay Associated With Human Activities and Environmental Governance
Authors: Cui Kaixuan , Dong Yi , Sun Xiaoxia , Zhao Li , Du Haijian , Liu Jia , Wang Chaofeng , Liang Chen , Zhao Yicong , Chen Si , Xuan Jun , Li Suheng , Zhao Yuan , Xiao Tian
Published: August 2021

Coliform bacteria (CB) can be used as an indicator of seawater quality. Long-term monitoring of seawater quality based on CB abundance is lacking in Jiaozhou Bay. In this study, CB abundance in surface seawater of 12 different stations in Jiaozhou Bay was investigated by culturing method. The results showed that: (1) the abundance of CB showed a decreasing tendency during the investigation. During 2004–2007, 2008–2013, and 2014–2017, the average CB abundance decreased significantly, forming a “three stages phenomenon”; (2) the average CB abundance in the first half of the year was lower than that in the second half; (3) the CB abundance in Jiaozhou Bay was spatially heterogeneous. The maximum average CB abundance was observed in the estuary area, and followed by the bay mouth area, the outer bay area, and the inner bay area. The highest abundance may be associated with sewage discharge related to human activities; (4) the abundance of CB was most positively correlated with the concentration of ammonium salt and nitrate, while most negatively correlated with salinity; (5) the years 2007 (2008) and 2013 (2014) were time points of the “three stages phenomenon.” These time points coincide with environmental governance actions, indicating that the actions have played a prominent role in improving seawater quality. Long-term survey of CB can not only serve as an indicator of seawater quality, but also provide a basis for the development of environmental governance strategies and pollution control.
The Effects of Temperature Acclimation on Swimming Performance in the Pelagic Mahi-Mahi (Coryphaena hippurus)
Authors: Heuer Rachael M. , Stieglitz John D. , Pasparakis Christina , Enochs Ian C. , Benetti Daniel D. , Grosell Martin
Published: August 2021

Mahi-mahi (Coryphaena hippurus) are a highly migratory pelagic fish, but little is known about what environmental factors drive their broad distribution. This study examined how temperature influences aerobic scope and swimming performance in mahi. Mahi were acclimated to four temperatures spanning their natural range (20, 24, 28, and 32°C; 5–27 days) and critical swimming speed (Ucrit), metabolic rates, aerobic scope, and optimal swim speed were measured. Aerobic scope and Ucrit were highest in 28°C-acclimated fish. 20°C-acclimated mahi experienced significantly decreased aerobic scope and Ucrit relative to 28°C-acclimated fish (57 and 28% declines, respectively). 32°C-acclimated mahi experienced increased mortality and a significant 23% decline in Ucrit, and a trend for a 26% decline in factorial aerobic scope relative to 28°C-acclimated fish. Absolute aerobic scope showed a similar pattern to factorial aerobic scope. Our results are generally in agreement with previously observed distribution patterns for wild fish. Although thermal performance can vary across life stages, the highest tested swim performance and aerobic scope found in the present study (28°C), aligns with recently observed habitat utilization patterns for wild mahi and could be relevant for climate change predictions.
Catch and Length Models in the Stock Synthesis Framework: Expanded Application to Data-Moderate Stocks
Authors: Rudd Merrill B. , Cope Jason M. , Wetzel Chantel R. , Hastie James
Published: August 2021

Many fisheries in the world are data-moderate, with data types (e.g., total removals, abundance indices, and biological composition data) of varied quality (e.g., limited time series or representative samples) or available data. Integrated stock assessments are useful tools for data-moderate fisheries as they can include all available information, can be updated due to the availability of more information over time, and can directly test the inclusion and exclusion of specific data types. This study uses the simulation testing and systematic data reduction from the US West Coast benchmark assessments to examine the performance of Stock Synthesis with catch and length (SS-CL) compositions only. The simulation testing of various life histories, recruitment variabilities, and data availability scenarios found that the correctly specified SS-CL can estimate unbiased key population quantities such as stock status with as little as 1 year of length data although 5 years or more may be more reliable. The error in key population quantities is decreased with an increase in years and the sample size of length data. The removal of the length compositions from benchmark assessments often caused large model deviations in the outputs compared to the removal of other data sources, indicating the importance of length data in integrated models. Models with catch and length data, excluding abundance indices and age composition, generally provided informative estimates of the stock status relative to the reference model, with most data scenarios falling within the CIs of the reference model. The results of simulation analysis and systematic data reduction indicated that SS-CL is potentially viable for data-moderate assessments in the USA, thus reducing precautionary buffers on catch limits for many stocks previously assessed in a lower tier using catch-only models. SS-CL could also be applied to many stocks around the world, maximizing the use of data available via the well tested, multifeature benefits of SS.
Reef Conservation off the Hook: Can Market Interventions Make Coral Reef Fisheries More Sustainable?
Authors: Cramer Katie L. , Kittinger John N.
Published: August 2021

The overexploitation of coral reef fisheries threatens the persistence of reef ecosystems and the livelihoods and food security of millions of people. Market-based initiatives to increase fisheries sustainability have been widely implemented in industrialized commodity fisheries, but the suitability of these initiatives for coral reef fisheries has not been systematically investigated. Here, we present a typology of market-based interventions and coral reef fisheries sectors and identity promising approaches for each fishery archetype. For high value, export-oriented reef fisheries that are highly unsustainable (live reef food fish and dried sea cucumbers), traditional regulatory efforts including trade restrictions will be most effective. For high-value, export-oriented fisheries for highly fecund invertebrates (lobsters and mollusks), certification and ratings efforts, fishery improvement projects, and sustainable purchasing commitments can improve fishing practices and increase fisher market access and revenue. For lower-value fisheries targeting species for domestic or regional consumption, sustainable purchasing commitments among local buyers, consumer awareness campaigns, and local certification and ratings schemes hold promise for shifting attitudes toward sustainability and increasing food security for local communities. Finally, fisher empowerment efforts including direct access to local markets and market information, training on improved post-harvest methods, and formation of fisher associations hold promise for increasing fisher incomes, reducing wasteful catch, increasing food security, and de-incentivizing unsustainable practices. Despite the potential of market-based interventions, specific approaches must be carefully tailored to the ecological and social reality of these systems, including the inherent unsustainability of commercial coral reef fisheries, the limited capacity for fisheries governance, the limited financial support of market-based initiatives, and the threatened status of coral reef ecosystems globally.
Effects of Dietary Silica Nanoparticle on Growth Performance, Protein Digestibility, Hematology, Digestive Morphology, and Muscle Composition of Nile Tilapia, Oreochromis Niloticus
Authors: Bashar Abul , Hasan Neaz A. , Haque Mohammad Mahfujul , Rohani Md. Fazle , Hossain Md. Sazzad
Published: August 2021

The use of nanotechnology in food production systems is being investigated globally, though there is limited research on its effect on fish nutrition. Therefore, this study aimed to identify the effects of silica nanoparticles (NPs) on the nutrition and physiology of tilapia, Oreochromis niloticus. Four isonitrogenous diets (300 g/kg crude protein) with NPs (0, 1, 2, and 3 mg/kg diet) were fed to fish (6.52 ± 0.20 g) in a recirculatory aquaculture system for 56 days. Throughout the study period, the effects of silica NP on survival rate, blood cell count, hemoglobin (Hb) level, condition factor (CF), and final product composition (except lipid content) were insignificant. However, growth performance and feed efficiency increased with an increasing level of silica NP, up to 2 mg/kg, and then decreased. This increase was due to the highest apparent protein digestibility and dry matter digestibility when fish were fed silica NP at 2 mg/kg. However, fish at the early stage showed better performance in all dietary groups than in later. Blood glucose (BG) content and histology of the kidney revealed that fish were stressed when a 3 mg/kg silica NP was used and they adapted through excessive excretion via expanded glomeruli. Though no significant effect on villi length was observed, silica NP increased the surface area widening the villi of the gut along with the number of goblet cells in the intestine significantly, when supplemented at a level of 2 mg/kg. The bioaccumulation of silica shows that incorporating silica NP in the fish feed will not compromise human health safety upon consumption. Although silica NP at 1 mg/kg and 3 mg/kg yielded some improvements to growth and final product quality, a 2 mg/kg silica NP generated the best results in all measured parameters.
Metagenomic Insights Into Ecosystem Function in the Microbial Mats of a Large Hypersaline Coastal Lagoon System
Authors: Walter Juline Marta , de Oliveira Louisi Souza , Tschoeke Diogo Antonio , Meirelles Pedro Milet , Neves Maria Helena Campos Baeta , Batista Daniela , Carvalho Ana Polycarpa , Santos Costa Rafaela Dos , Dobretsov Sergey , Coutinho Ricardo , Swings Jean , Thompson Cristiane Carneiro , Thompson Fabiano L.
Published: August 2021

The hypersaline lagoon system of Araruama (HLSA) is one of the largest in the world and one of the most important sources of evaporative salt in Brazil. The biogeochemical characteristics of this lagoon system led it to be considered a Precambrian relic. The HLSA also harbors extensive microbial mats, but the taxonomic and metabolic attributes of these mats are poorly understood. Our high-throughput metagenomics analyses demonstrated that the HLSA microbial mats are dominated by Proteobacteria, Cyanobacteria, and Bacteroidetes. Among Proteobacteria, Deltaproteobacteria comprises approximately 40% of the total population and it includes sulfate-reducing bacteria such as Desulfobacterales, Desulfuromonadales, and Desulfovibrionales. Differing in composition and function of their reaction centers, other phylogenetic diverse anoxygenic phototrophic bacteria were detected in the HLSA microbial mats metagenomes. The presence of photolithoautotrophs, sulfate reducers, sulfide oxidizers, and aerobic heterotrophs suggests the existence of numerous cooperative niches that are coupled and regulated by microbial interactions. We suggest that the HLSA microbial mats hold microorganisms and the necessary machinery (genomic repertoire to sustain metabolic pathways) to promote favorable conditions (i.e., create an alkaline pH microenvironment) for microbially mediated calcium carbonate precipitation process. Metagenome-assembled genomes (Ca. Thiohalocapsa araruaensisHLSAbin6 sp. nov. andCa. Araruabacter turfaeHLSAbin9 gen. nov. sp. nov.) obtained support the relevance of Sulfur metabolism and they are enriched with genes involved in the osmoadaptive networks, hinting at possible strategies to withstand osmotic stress. Metabolically versatile bacteria populations, able to use multiple nutrient sources and osmolytes, seem to be a relevant attribute to survive under such stressful conditions.
Poro-Viscoelastic Effects During Biomechanical Testing of Human Brain Tissue
Authors: Greiner Alexander , Reiter Nina , Paulsen Friedrich , Holzapfel Gerhard A. , Steinmann Paul , Comellas Ester , Budday Silvia
Published: August 2021

Brain tissue is one of the softest tissues in the human body and the quantification of its mechanical properties has challenged scientists over the past decades. Associated experimental results in the literature have been contradictory as characterizing the mechanical response of brain tissue not only requires well-designed experimental setups that can record the ultrasoft response, but also appropriate approaches to analyze the corresponding data. Due to the extreme complexity of brain tissue behavior, nonlinear continuum mechanics has proven an expedient tool to analyze testing data and predict the mechanical response using a combination of hyper-, visco-, or poro-elastic models. Such models can not only allow for personalized predictions through finite element simulations, but also help to comprehensively understand the physical mechanisms underlying the tissue response. Here, we use a nonlinear poro-viscoelastic computational model to evaluate the effect of different intrinsic material properties (permeability, shear moduli, nonlinearity, viscosity) on the tissue response during different quasi-static biomechanical measurements, i.e., large-strain compression and tension as well as indentation experiments. We show that not only the permeability but also the properties of the viscoelastic solid largely control the fluid flow within and out of the sample. This reveals the close coupling between viscous and porous effects in brain tissue behavior. Strikingly, our simulations can explain why indentation experiments yield that white matter tissue in the human brain is stiffer than gray matter, while large-strain compression experiments show the opposite trend. These observations can be attributed to different experimental loading and boundary conditions as well as assumptions made during data analysis. The present study provides an important step to better understand experimental data previously published in the literature and can help to improve experimental setups and data analysis for biomechanical testing of brain tissue in the future.
Translational Research Studies Unraveling the Origins of Psoriatic Arthritis: Moving Beyond Skin and Joints
Authors: Bolt Janne W. , van Ansenwoude Chaja M. J. , Hammoura Ihsan , van de Sande Marleen G. , van Baarsen Lisa G. M.
Published: August 2021

Patients with psoriatic arthritis (PsA) are suffering from a decreased quality of life despite currently available treatments. In the latest years, novel therapies targeting the IL-17/IL-23 and TNF pathways improved clinical outcome. Despite this, remission of disease is not achieved in a considerable group of patients, continuous treatment is very often required to reach clinical remission, and prevention of PsA in patients with psoriasis (PsO) is currently impossible. A better understanding of PsA pathogenesis is required to develop novel treatment strategies that target inflammation and destruction more effectively and at an early stage of the disease, or even before clinically manifest disease. The skin is considered as one of the sites of onset of immune activation, triggering the inflammatory cascade in PsA. PsO develops into PsA in 30% of the PsO patients. Influenced by environmental and genetic factors, the inflammatory process in the skin, entheses, and/or gut may evolve into synovial tissue inflammation, characterized by influx of immune cells. The exact role of the innate and adaptive immune cells in disease pathogenesis is not completely known. The involvement of activated IL-17A+ T cells could implicate early immunomodulatory events generated in lymphoid organs thereby shaping the pathogenic inflammatory response leading to disease. In this perspective article, we provide the reader with an overview of the current literature regarding the immunological changes observed during the earliest stages of PsA. Moreover, we will postulate future areas of translational research aimed at increasing our knowledge on the molecular mechanisms driving disease development, which will aid the identification of novel potential therapeutic targets to limit the progression of PsA.
[18F]FDG Positron Emission Tomography for Initial Staging and Healing Assessment at the End of Therapy in Lymph Nodes and Bone Tuberculosis
Authors: Sarda-Mantel Laure , Kaoutar Jidar , Alfaiate Toni , Lopes Amanda , Paycha Frédéric , Benali Khadija , Mikail Nidaa , Soussan Michael , Lemarignier Charles , Méchaï Frédéric , Nagat Sophie Le , Montravers Françoise , Deradji Ouda , Durand Emmanuel , Goulenok Tiphaine , Ponscarme Diane , Yéni Patrick , Laouénan Cédric , Rioux Christophe
Published: August 2021

Objective: In extra-pulmonary tuberculosis, therapeutic management is difficult in the absence of reliable tool to affirm healing at the end of treatment. In this prospective multicenter study, we evaluated [18F]FDG-PET for this purpose.

Methods: Forty-two patients out of 55 included patients could be analyzed. Additionally to usual biological, histological and morphological explorations, [18F]FDG-PET was performed at diagnosis (PET1), at the end of treatment (PET2), indeed 6 months later. Then patients were followed until 12 months after end of prescribed treatment.

Results: PET1 was positive in 97.6% of patients and discovered unknown injured sites in 52.7% of cases. PET2 was positive in 83.3% of uncured patients, and in 82.3% of cured patients. The sum and mean value of SUVmax measured in PET/CT lesions decreased between PET1 and PET2 in all patients. Mean value of SUVmax (MSUV) and sum value of SUVmax on PET2 showed the highest AUC on ROC curves for the diagnosis of healing at the end of prescribed treatment; MSUV 3.5 on PET2 had a sensitivity of 76.5% and a specificity of 80.0% to affirm healing at the end of prescribed treatment.

Conclusions: [18F]FDG-PET/CT was useful at diagnosis, discovering unknown lesions in 52.7% of cases. MSUV on PET2 was the best criteria to affirm healing at the end of prescribed treatment.