bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating Future Migration Flows Under Social and Environmental Scenarios Taking Into Account Interactions: Insights From a Survey Among Migration Scholars
Authors: Boissonneault Michaël , Wieke de Jong Petra
Published: June 2022

Scenario planning has been gaining popularity during the last decade as a tool for exploring how international migration flows might be affected by changing future circumstances. Using this technique, scholars have developed narratives that describe how flows might change depending on different developments in two of their most impactful and uncertain drivers. Current applications of scenario planning to migration however suffer from limitations that reduce the insights that can be derived from them. In this article, we first highlight these limitations by reviewing existing applications of scenario planning to migration. Then, we propose a new approach that consists in specifying different pathways of change in a set of six predefined drivers, to then ask migration scholars how each of these pathways might impact both migration flows and the other five drivers. We apply our approach to the case of migration pressure and demand from less developed countries to Europe until the year 2050. Results from our survey underscore the importance of a wide array of drivers for the future of migration that have so far not been considered in previous applications of scenario planning. They further suggest that drivers do not change independently from each other, but that specific changes in some drivers are likely to go hand in hand with changes in other drivers. Lastly, we find that changes in similar drivers could have different effects in sending and receiving countries. We finish by discussing how enhanced, quantified scenarios of migration between less developed countries and Europe can be formulated based on our results.
A Murine Point Mutation of Sgpl1 Skin Is Enriched With Vγ6 IL17-Producing Cell and Revealed With Hyperpigmentation After Imiquimod Treatment
Authors: Yang Wenyi , Zhou Binhui , Liu Qi , Liu Taozhen , Wang Huijie , Zhang Pei , Lu Liaoxun , Zhang Lichen , Zhang Fanghui , Huang Rong , Zhou Jitong , Chao Tianzhu , Gu Yanrong , Lee Songhua , Wang Hui , Liang Yinming , He Le
Published: June 2022

Sphingosine-1-phosphate lyase is encoded by the Sgpl1 gene, degrades S1P, and is crucial for S1P homeostasis in animal models and humans. S1P lyase deficient patients suffer from adrenal insufficiency, severe lymphopenia, and skin disorders. In this study, we used random mutagenesis screening to identify a mouse line carrying a missense mutation of Sgpl1 (M467K). This mutation caused similar pathologies as Sgpl1 knock-out mice in multiple organs, but greatly preserved its lifespan, which M467K mutation mice look normal under SPF conditions for over 40 weeks, in contrast, the knock-out mice live no more than 6 weeks. When treated with Imiquimod, Sgpl1M467K mice experienced exacerbated skin inflammation, as revealed by aggravated acanthosis and orthokeratotic hyperkeratosis. We also demonstrated that the IL17a producing Vγ6+ cell was enriched in Sgpl1M467K skin and caused severe pathology after imiquimod treatment. Interestingly, hyperchromic plaque occurred in the mutant mice one month after Imiquimod treatment but not in the controls, which resembled the skin disorder found in Sgpl1 deficient patients. Therefore, our results demonstrate that Sgpl1M467K point mutation mice successfully modeled a human disease after being treated with Imiquimod. We also revealed a major subset of γδT cells in the skin, IL17 secreting Vγ6 T cells were augmented by Sgpl1 deficiency and led to skin pathology. Therefore, we have, for the first time, linked the IL17a and γδT cells to SPL insufficiency.
Plasmodium vivax Protein PvTRAg23 Triggers Spleen Fibroblasts for Inflammatory Profile and Reduces Type I Collagen Secretion via NF-κBp65 Pathway
Authors: Zhang Hangye , Shen Feihu , Yu Jiali , Ge Jieyun , Sun Yifan , Fu Haitian , Cheng Yang
Published: June 2022

Plasmodium vivaxis the most widespread human malaria parasite. The spleen is one of the most significant immune organs in the course ofPlasmodiuminfection, and it contains splenic fibroblasts (SFs), which supports immunologic function by secreting type I collagen (collagen I).Plasmodiumproteins have rarely been found to be involved in collagen alterations in the spleen during infection. Here, we selected the proteinP. vivaxtryptophan-rich antigen 23 (PvTRAg23), which is expressed by the spleen-dependent genePv-fam-aand is a member of the PvTRAgs family of export proteins, suggesting that it might have an effect on SFs. The protein specifically reduced the level of collagen I in human splenic fibroblasts (HSFs) and bound to cells with vimentin as receptors. However, such collagen changes were not mediated by binding to vimentin, but rather activating the NF-κBp65 pathway to produce inflammatory cytokines. Collagen impaired synthesis accompanied by extracellular matrix-related changes occurred in the spleen of mice infected withP. yoelii17XNL. Overall, this study is the first one to report and verify the role ofPlasmodiumproteins on collagen in HSFin vitro. Results will contribute to further understanding of host spleen structural changes and immune responses afterPlasmodiuminfection.
The cGAS-STING Pathway Affects Vertebral Bone but Does Not Promote Intervertebral Disc Cell Senescence or Degeneration
Authors: Ottone Olivia K. , Kim C. James , Collins John A. , Risbud Makarand V.
Published: June 2022

The DNA-sensing cGAS-STING pathway promotes the senescence-associated secretory phenotype (SASP) and mediates type-I interferon inflammatory responses to foreign viral and bacterial DNA as well as self-DNA. Studies of the intervertebral disc in humans and mice demonstrate associations between aging, increased cell senescence, and disc degeneration. Herein we assessed the role of STING in SASP promotion in STING gain- (N153S) and loss-of-function mouse models. N153S mice evidenced elevated circulating levels of proinflammatory markers including IL-1β, IL-6, and TNF-α, showed elevated monocyte and macrophage abundance in the vertebral marrow, and exhibited a mild trabecular and cortical bone phenotype in caudal vertebrae. Interestingly, despite systemic inflammation, the structural integrity of the disc and knee articular joint remained intact, and cells did not show a loss of their phenotype or elevated SASP. Transcriptomic analysis of N153S tissues demonstrated an upregulated immune response by disc cells, which did not closely resemble inflammatory changes in human tissues. Interestingly, STING-/- mice also showed a mild vertebral bone phenotype, but the absence of STING did not reduce the abundance of SASP markers or improve the age-associated disc phenotype. Overall, the analyses of N153S and STING-/- mice suggest that the cGAS-STING pathway is not a major contributor to SASP induction and consequent disc aging and degeneration but may play a minor role in the maintenance of trabecular bone in the vertebrae. This work contributes to a growing body of work demonstrating that systemic inflammation is not a key driver of disc degeneration.
Single-Nucleotide Polymorphisms Within Non-HLA Regions Are Associated With Engraftment Effectiveness for Patients With Unrelated Cord Blood Transplantation
Authors: Chen Ding-Ping , Jaing Tang-Her , Hour Ai-Ling , Lin Wei-Tzu , Hsu Fang-Ping
Published: June 2022

Clinically, stem cells with matched human leukocyte antigens (HLAs) must be selected for allogeneic transplantation to avoid graft rejection. However, adverse reactions still occur after cord blood transplantation (CBT). It was inferred that the HLA system is not the only regulatory factor that may influence CBT outcomes. Therefore, we plan to investigate whether the single-nucleotide polymorphisms (SNPs) located in non-HLA genes are associated with the effectiveness of CBT. In this study, the samples of 65 donors from CBT cases were collected for testing. DNA sequencing was focused on the SNPs of non-HLA genes, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily 4 (TNFSF4), and programmed cell death protein 1 (PDCD1), which were selected in regard to the literatures published in 2017 and 2018, which indicated that they were related to stem cell transplantation. Then, in combination with the detailed follow-up transplantation tracking database, these SNPs were analyzed with the risk of mortality, relapse, cytomegalovirus (CMV) infection, and graft-versus-host disease (GVHD). We found that there were 2 SNPs of CTLA4, 1 SNP of TNFSF4, and 2 SNPs of PDCD1 associated with the effectiveness of unrelated CBT. These statistically significant SNPs and haplotypes would be used in clinical to choose the best donor for the patient receiving CBT. Moreover, the polygenic risk scores (PRSs) with these SNPs could be used to predict the risk of CBT adverse reactions with an area under the receiver operating characteristic curve (AUC) of 0.7692. Furthermore, these SNPs were associated with several immune-related diseases or cancer susceptibility, which implied that SNPs play an important role in immune regulation.
A TNFR2-Specific TNF Fusion Protein With Improved In Vivo Activity
Authors: Vargas Juan Gamboa , Wagner Jennifer , Shaikh Haroon , Lang Isabell , Medler Juliane , Anany Mohamed , Steinfatt Tim , Mosca Josefina Peña , Haack Stephanie , Dahlhoff Julia , Büttner-Herold Maike , Graf Carolin , Viera Estibaliz Arellano , Einsele Hermann , Wajant Harald , Beilhack Andreas
Published: June 2022

Tumor necrosis factor (TNF) receptor-2 (TNFR2) has attracted considerable interest as a target for immunotherapy. Indeed, using oligomeric fusion proteins of single chain-encoded TNFR2-specific TNF mutants (scTNF80), expansion of regulatory T cells and therapeutic activity could be demonstrated in various autoinflammatory diseases, including graft-versus-host disease (GvHD), experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA). With the aim to improve the in vivo availability of TNFR2-specific TNF fusion proteins, we used here the neonatal Fc receptor (FcRn)-interacting IgG1 molecule as an oligomerizing building block and generated a new TNFR2 agonist with improved serum retention and superior in vivo activity.

Methods

Single-chain encoded murine TNF80 trimers (sc(mu)TNF80) were fused to the C-terminus of an in mice irrelevant IgG1 molecule carrying the N297A mutation which avoids/minimizes interaction with Fcγ-receptors (FcγRs). The fusion protein obtained (irrIgG1(N297A)-sc(mu)TNF80), termed NewSTAR2 (New selective TNF-based agonist of TNF receptor 2), was analyzed with respect to activity, productivity, serum retention and in vitro and in vivo activity. STAR2 (TNC-sc(mu)TNF80 or selective TNF-based agonist of TNF receptor 2), a well-established highly active nonameric TNFR2-specific variant, served as benchmark. NewSTAR2 was assessed in various in vitro and in vivo systems.

Results

STAR2 (TNC-sc(mu)TNF80) and NewSTAR2 (irrIgG1(N297A)-sc(mu)TNF80) revealed comparable in vitro activity. The novel domain architecture of NewSTAR2 significantly improved serum retention compared to STAR2, which correlated with efficient binding to FcRn. A single injection of NewSTAR2 enhanced regulatory T cell (Treg) suppressive activity and increased Treg numbers by > 300% in vivo 5 days after treatment. Treg numbers remained as high as 200% for about 10 days. Furthermore, a single in vivo treatment with NewSTAR2 upregulated the adenosine-regulating ectoenzyme CD39 and other activation markers on Tregs. TNFR2-stimulated Tregs proved to be more suppressive than unstimulated Tregs, reducing conventional T cell (Tcon) proliferation and expression of activation markers in vitro. Finally, singular preemptive NewSTAR2 administration five days before allogeneic hematopoietic cell transplantation (allo-HCT) protected mice from acute GvHD.

Conclusions

NewSTAR2 represents a next generation ligand-based TNFR2 agonist, which is efficiently produced, exhibits improved pharmacokinetic properties and high serum retention with superior in vivo activity exerting powerful protective effects against acute GvHD.
Standardization of Antigen-Emulsion Preparations for the Induction of Autoimmune Disease Models
Authors: Topping Louise M. , Romero-Castillo Laura , Urbonaviciute Vilma , Bolinsson Hans , Clanchy Felix I. , Holmdahl Rikard , Bäckström B. Thomas , Williams Richard O.
Published: June 2022

Autoimmune murine disease models are vital tools for identifying novel targets and finding better treatments for human diseases. Complete Freund’s adjuvant is commonly used to induce disease in autoimmune models, and the quality of the adjuvant/autoantigen emulsion is of critical importance in determining reproducibility. We have established an emulsification method using a standard homogenizer and specially designed receptacle. Emulsions are easy to prepare, form stable and uniform water-in-oil particles, are faster to make than the traditional syringe method, use less material and are designed to fill syringes with ease. In the present study, we have validated the emulsions for induction of experimental autoimmune encephalitis, collagen II induced arthritis, antigen induced arthritis, and delayed type hypersensitivity models. These models were induced consistently and reproducibly and, in some cases, the new method outperformed the traditional method. The method described herein is simple, cost-effective and will reduce variability, thereby requiring fewer animals forin vivoresearch involving animal models of autoimmune disease and in vaccine development.
Oral Administration of a Shigella 2aT32-Based Vaccine Expressing UreB-HspA Fusion Antigen With and Without Parenteral rUreB-HspA Boost Confers Protection Against Helicobacter pylori in Mice Model
Authors: Zhang Xin , Sang Shuli , Guan Qing , Tao Haoxia , Wang Yanchun , Liu Chunjie
Published: June 2022

Helicobacter pylori (H. pylori) is a gram-negative pathogen classified as a class I carcinogen. The H. pylori urease B subunit (UreB) and heat shock protein A (HspA) are two important vaccine candidate antigens. In this study, we evaluated the immunogenicity and immunoprotective effect of the attenuated Shigella vector vaccine SH02 expressing the UreB-HspA fusion protein of H. pylori in a mouse model. Oral SH02 with or without subcutaneous injection of rUreB-HspA induced antigen-specific serum IgG, mucosal sIgA, and T cells immune response. Subcutaneous injection of the candidate antigen rUreB-HspA enhanced the level of serum antigen-specific IgG antibodies (p < 0.0001) and the levels of IgG1/IgG2a/IgG2b subtypes. In addition, injection boost also increased the proportion of spleen antigen-specific CD4+CD154+ T cells (p < 0.001), and the proportion of CD4+CD154+ T cells that secrete IFN-γ and IL-17A. Following the H. pylori challenge, the levels of H. pylori colonization in the two experimental groups (Groups A and B) significantly reduced compared with the control group (p < 0.001), indicating that the candidate vaccine yielded a preventive effect of anti-H.pylori infection. Compared with the non-subcutaneous booster injection group (Group A), the subcutaneous booster injection group (Group B) exhibited less gastric inflammation, but there was no significant difference in the level of colonization (p > 0.05). These results lay a foundation for the development of a vaccine against H. pylori and the optimization of immunization methods and procedures to prevent H. pylori infection.
Biological Characteristics of HLA-G and Its Role in Solid Organ Transplantation
Authors: Liu Siqi , Bos Nicolaas A. , Verschuuren Erik A. M. , van Baarle Debbie , Westra Johanna
Published: June 2022

Organ transplantation is a lifesaving option for patients with advanced diseases. Rejection is regarded as one of the most severe risk factors post-transplantation. A molecule that contributes to immune tolerance and resisting rejection is human leukocyte antigen (HLA)-G, which belongs to the non-classical major histocompatibility complex class (MHC) I family. HLA-G was originally found to play a role during pregnancy to maintain immune tolerance between mother and child. It is expressed in the placenta and detected in several body fluids as soluble factor as well as different membrane isoforms on cells. Recent findings on HLA-G show that it can also play multifaceted roles during transplantation. This review will explain the general characteristics and biological function of HLA-G and summarize the views supporting the tolerogenic and other roles of HLA-G to better understand its role in solid organ transplantation (SOT) and its complications. Finally, we will discuss potential future research on the role of HLA-G in prevention, diagnosis, and treatment in SOT.
To Be or Not to Be: The Case of Endoplasmic Reticulum Aminopeptidase 2
Authors: Kuśnierczyk Piotr
Published: June 2022

To be, or not to be, that is the question. (William Shakespeare, Hamlet)

Endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2, respectively) play a role in trimming peptides that are too long to be bound and presented by class I HLA (HLA-I) molecules to CD8+T cells. They may also affect the HLA-I-presented peptide repertoire by overtrimming potential epitopes. Both enzymes may also be released from the cell to cleave cytokine receptors and regulate blood pressure. Both enzymes are polymorphic, which affects their expression, specificity, and activity, resulting in their role in diseases associated with HLA-I. In this brief review, we concentrate on ERAP2, less investigated because of its lack in laboratory mice and 25% of humans, as well as a lower polymorphism. ERAP2 was found to be associated with several diseases and to influence ERAP1 effects. It was discovered recently that the defectiveERAP2gene, not encoding functional aminopeptidase, may nevertheless, during viral infections, produce a truncated protein isoform of unknown function, possibly interfering with ERAP1 and full-length ERAP2 by heterodimer formation. The disease associations of ERAP2, alone or in combination with ERAP1, are reviewed.
B10 Cells Are Associated With Clinical Prognosis During Adult Symptomatic Acute HBV Infection
Authors: Liu Yali , Du Xiaofei , Lu Junfeng , Ma Lina , Jing Yi , Ben Haijing , Chen Xinyue , Zhang Jing
Published: June 2022

There are few reports about the role of B10 cells in acute hepatitis B (AHB) infection. In this study, based on 48 acute hepatitis B infected patients, we analysis the correlation of B10 cells with HBV clinical prognosis. The results showed that B10 was positively correlated with HBsAg and HBeAg and inversely correlated with anti-HBs. The level of B10 in one week before HBsAg clearance was significantly lower than 2 weeks prior to HBsAg clearance and after 1-2 weeks of HBsAg clearance. B10 cell frequency displayed no correlation with HBV DNA; however, it showed significant temporal synchronization with hepatic inflammatory markers such as ALT. B10 level also associated with hospitalization time. These results indicated that B10 is closely related to the clinical prognosis of acute HBV infection.
Habitat and Marine Reserve Status Drive Reef Fish Biomass and Functional Diversity in the Largest South Atlantic Coral Reef System (Abrolhos, Brazil)
Authors: Rolim Fernanda Andreoli , Langlois Tim , Motta Fábio dos Santos , Castro Guilherme Malagutti de , Lester Emily , Abieri Maria Luiza , Gadig Otto Bismarck Fazzano , Moura Rodrigo Leão de
Published: June 2022

The effects of fishing have been documented across coral reefs worldwide. No-take marine reserves do not only act as a conservation tool but also allow an opportunity to study impacts of fishing, by acting as control sites. In addition, well-planned and well-managed no-take marine reserves (NTRs) provide conservation benefits that are essential to marine biodiversity and ecosystem-based management. The Abrolhos Marine National Park, off the tropical Brazilian coast, protects part of the largest coral reef system in the South Atlantic. To investigate the effects of fishing on reef fish richness, abundance, biomass, and functional diversity of the fish assemblage, we compared sites across two protection levels considering the variation in habitats (Fringing Reefs—Protected; Pinnacles Reefs—Protected; and Coastal Reefs—Open Access), using Baited Remote Underwater Stereo-Video systems (stereo-BRUVs). We adjusted generalized additive mixed models of fish assemblage characteristics with protection levels and environmental variables, such as topographic complexity (mean relief and relief variation), visibility, and benthic cover percentage. Inside NTRs, we found higher total biomass and biomass of fishery target species and carnivores, specifically for the Carcharhinidae (sharks) and Epinephelidae (groupers) families, indicating direct fisheries effects on these groups. In contrast, the ecological parameters of non-target fish were positively correlated with habitat characteristics, including mean relief and variance of relief. Moreover, fish functional diversity was higher within NTRs, demonstrating an even distribution of functional entities. The presence of large mobile predators and the overall higher biomass of carnivores inside the NTR indicate the effect of fishing exclusion. Our results point to the value of NTRs to study the effects of fishing and achieve biodiversity conservation and suggest the importance of using remote sampling methods to assess large mobile predators.
Influence of Chemoautotrophic Organic Carbon on Sediment and Its Infauna in the Vicinity of the Rainbow Vent Field
Authors: Roohi Reyhaneh , Hoogenboom Ragna , Van Bommel Ronald , Van Der Meer Marcel T. J. , Mienis Furu , Gollner Sabine
Published: June 2022

Hydrothermal vents have been recognised as isolated islands of productivity in the deep sea, but very little is known about the transport and export of chemoautotrophic produced organic carbon to vent surrounding habitats. Here, we investigate vent carbon export and its influence on benthic food webs in sediments at the Rainbow (RB) vent field at the Mid Atlantic Ridge in ~2200 m water depth. Two sites were considered along the dispersal direction of the RB vent plume for sample collection: the close vicinity at about ~30-100 m (“near-vent”); and at 4 km distance (“off-vent”) to the nearest venting area. At both sites, box corers were used to sample sediments and their fauna. A turbidity sensor mounted on a CTD/Rosette provided data on the presence of a vent fluid plume in the water column. Niskin bottles were used to sample suspended particulate organic matter (SPOM) from the plume, as well as from surface waters at 75 m depth. SPOM, sediments and fauna were analysed for nitrogen and carbon stable isotopes. Carbon derived from in situ chemoautotrophy, characterised by depleted δ13C, was taken up by infauna close to the venting area as the main nutrition source, while fauna at the off-vent site showed less depleted δ13C with a signature more typical for photosynthetic- derived material. Nematodes were the most abundant faunal taxon. Their abundance and biomass were variable and not different at the two studied sites. In situ derived organic matter was traced back in the food web in the close vicinity of the venting area. The connectivity of vent and non-vent habitats should be taken appropriately into account when designing future spatial management plans with regard to deep-seabed mining at hydrothermal vents.
Extreme Value Analysis of Ocean Currents in the Mexican Caribbean Based on HYCOM Numerical Model Data
Authors: Ring Michael , Rodríguez-Ocampo Paola Elizabeth , Silva Rodolfo , Mendoza Edgar
Published: June 2022

Comprehensive knowledge of extreme values is required for designing offshore structures and ocean current turbines. However, data on the return levels of ocean currents are rarely available. This is the case for the Mexican Caribbean, where enormous energy potential in the ocean currents has recently been detected. In this study, long-term numerical data from the Hybrid Coordinate Ocean Model for a depth of 50m was adjusted via linear quantile regression to short-term empirical data for a depth of 49m. The error of the results was estimated using simplified extreme value analysis. Based on the numerical data, a comprehensive extreme value analysis was conducted using the peaks over threshold method and fitting a Generalized Pareto Distribution to the data. This method relies on filtering peaks with a moving time window and an automated threshold selection based on a reparameterised scale parameter of the Generalized Pareto Distribution. The adjusted numerical model is shown to underestimate the empirical data with the error converging to almost 22% for rare events (return period > 10years). The method showed consistent results in the domain, with some anomalies only at the boundaries of the underlying numerical model. The methodology is suitable for estimating the return levels of ocean currents provided by HYCOM, although further research is needed to reduce the error of the numerical model.
Benthic-Pelagic Coupling of Marine Primary Producers Under Different Natural and Human-Induced Pressures’ Regimes
Authors: Gerakaris Vasilis , Varkitzi Ioanna , Orlando-Bonaca Martina , Kikaki Katerina , Mozetič Patricija , Lardi Polytimi-Ioli , Tsiamis Konstantinos , Francé Janja
Published: June 2022

Marine primary producers are highly sensitive to environmental deterioration caused by natural and human-induced stressors. Following the Water Framework Directive and the Marine Strategy Framework Directive requirements, the importance of using the different primary producers of the coastal marine ecosystem (pelagic: phytoplankton and benthic: macroalgae and angiosperms) as appropriate tools for an integrated assessment of the ecological status of the coastal environment has been recognized. However, the processes by which water column characteristics and phytobenthic indicators are linked have not been systematically studied. Based on a large dataset from three Mediterranean sub-basins (Adriatic, Ionian and Aegean Seas) with different trophic conditions, this study aims to explore the coupled responses of benthic and pelagic primary producers to eutrophication pressures on a large scale, focusing on the structural and functional traits of benthic macroalgal and angiosperm communities, and to investigate the key drivers among the different eutrophication-related pelagic indicators (such as nutrient and Chl-a concentrations, water transparency, etc.) that can force the benthic system indicators to low ecological quality levels. In addition to the effects of high nutrient loading on phytoplankton biomass, our results also show that increased nutrient concentrations in seawater have a similar effect on macroalgal communities. Indeed, increasing nutrient concentrations lead to increased coverage of opportunistic macroalgal species at the expense of canopy-forming species. Most structural traits ofPosidonia oceanica(expressed either as individual metrics: shoot density, lower limit depth and lower limit type, or in the context of PREI index) show opposite trends to increasing levels of pressure indicators such as ammonium, nitrate, phosphate, Chl-a and light attenuation. Furthermore, our results highlight the regulating effect of light availability on the ecological status of seagrass meadows (Posidonia oceanicaandCymodocea nodosa). Increasing leaf length values ofC. nodosaare closely associated with higher turbidity values linked to higher phytoplankton biomass (expressed as Chl-a). Overall, the coupling of pelagic and benthic primary producers showed consistent patterns across trophic gradients at the subregional scale.
Ecological Distribution and Diversity of Key Functional Genes for Denitrification in Surface Sediments of the Northern South China Sea: Implications for Potential N2O Emissions
Authors: Xiang Hua , Hong Yiguo , Wu Jiapeng , Long Aimin
Published: June 2022

Denitrification is an important pathway for nitrogen sink and N2O emissions, but little is known about the ecological distribution of key functional genes of denitrification and their potential N2O emissions in marine sediments. In this study, we analyzed the abundance, ecological distribution, and diversity of key functional genes (nir and nosZ) for denitrification in the northern South China Sea (SCS) surface sediments. Our results showed that the gene abundances varied from 105 to 108 and from 106 to 107 copies·g-1 for the nirS and nirK, respectively. The nosZ II/nosZ I gene abundance ratios were 1.28–9.88 in shallow-sea and deep-sea sediments, suggesting that the nosZ II gene should play a dominant role in N2O reduction in the northern SCS sediments. Moreover, the significantly higher abundance ratios of nir/nosZ in deep-sea surface sediments implied that there might be stronger N2O emissions potential in deep-sea sediments than in shallow-sea sediments. The ecological distribution profiles of the nirS, nosZ I, and nosZ II gene communities varied with water depth, and denitrification genes in shallow-sea and deep-sea sediments differed in their sensitivity to environmental factors. Water temperature was the major factor affecting both the abundance and the community distribution of the nirS gene in deep-sea sediments. Nitrate was the major factor shaping the community of nosZ I and nosZ II genes in shallow-sea sediments. Our study provides a pattern of ecological distribution and diversity for the nir and nosZ genes and emphasizes the role of these key functional genes in potential N2O emissions of the northern SCS surface sediments.
Experimental Study and Simulation on the Seal Pressure of a Ferrofluid Seal Using Radial-Charged Magnets
Authors: Liu Jiawei , Li Decai , Zhang Zhili
Published: June 2022

As one of the most mature applications of ferrofluid, the pole shoes of a ferrofluid seal are easily damaged under the situation of the large radial beating of the main shaft. Meanwhile, due to the small size, the pole teeth commonly used in pole shoes harbor problems such as poor processability and low seal pressure under a large gap. In order to solve the aforementioned problems, we proposed a new structure of the ferrofluid seal that uses a radial-charged ring magnet as the magnetic source. Then, considering that the ring magnets have problems of uneven magnetization and installation difficulties, we used split magnets to take the place of ring magnets and proposed the second new structure. According to the study on the distribution of magnetic field in seal gap axially and circumferentially, we obtained the simulation results of the two new structures’ seal pressure. The results revealed that the new structure of the ferrofluid seal with rectangular magnets can solve the aforementioned problems and exhibited a certain amount of sealing pressure.
Plasma Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in the Acute Respiratory Distress Syndrome
Authors: Metkus Thomas S. , Kim Bo Soo , Jones Steven R. , Martin Seth S. , Schulman Steven P. , Leucker Thorsten M.
Published: June 2022

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is a mediator of the immune response to sepsis. PCSK9 is also highly expressed in pneumocytes and pulmonary endothelial cells. We hypothesized that serum PCSK9 levels would be associated with death and ICU outcomes in patients with ARDS.

Methods

Using data and plasma samples from the NIH BioLINCC data repository, we assembled a cohort of 1,577 patients with the acute respiratory distress syndrome (ARDS) enrolled in two previously completed clinical trials, EDEN and SAILS. We measured PCSK9 levels in plasma within 24 h of intubation using commercially available ELISA kits (R&D Systems). We assessed the association of PCSK9 with mortality using Cox proportional hazard models. We also assessed clinical factors associated with PCSK9 level and the association of PCSK9 with the number of days free of mechanical ventilation and days free of ICU care.

Results

In 1,577 ARDS patients, median age was 53 years (IQR 42–65 years) and median APACHE III score 91 (72–111) connoting moderate critical illness. PCSK9 levels were 339.3 ng/mL (IQR 248.0–481.0). In multivariable models, race, cause of ARDS, body mass index, pre-existing liver disease, body temperature, sodium, white blood cell count and platelet count were associated with PCSK9 level. Presence of sepsis, use of vasopressors and ventilator parameters were not associated with PCSK9 level. PCSK9 levels were not associated with in-hospital mortality (HR per IQR 0.96, 95% CI 0.84–1.08, P = 0.47). Higher PCSK9 levels were associated with fewer ICU and ventilator free days.

Conclusions

Plasma PCSK9 is not associated with mortality in ARDS, however higher PCSK9 levels are associated with secondary outcomes of fewer ICU free and ventilator free days. Clinical factors associated with PCSK9 in ARDS are largely unmodifiable. Further research to define the mechanism of this association is warranted.
High Grade Dermatologic Adverse Events Associated With Immune Checkpoint Blockade for Cancer
Authors: Kuo Alyce M. , Markova Alina
Published: June 2022

Immune checkpoint blockade (ICB) improves survival in many types of cancers including melanoma, non-small cell lung, renal cell, breast, and cervical cancers. However, many of these therapies are also associated with high grade dermatologic adverse events (DAEs), including Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), SJS/TEN-like reactions, high grade maculopapular and psoriasiform rashes, autoimmune bullous eruptions, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which may limit their tolerability and use. It is important to properly identify and treat DAEs to ICB because these DAEs may be associated with positive anti-tumor response and patients may have limited options for alternative anti-cancer therapeutics. In this review, we describe high grade DAEs to increasingly used ICB agents, which target CTLA-4 and PD-1 or its ligand, PD-L1 and enable the immune system to target cancer cells. We further differentiate life-threatening adverse reactions from mimickers and report cases of serious DAEs which have been recorded in association with ICB through the FDA Adverse Events Reporting System (FAERS), which is an archive of adverse events associated with various drugs and therapeutic biologic products reported voluntarily by consumers and healthcare professionals as well as mandatorily by manufacturers. Lastly, we summarize management recommendations for these adverse events and discuss knowledge and evidence gaps in this area.
Water Deficit History Selects Plant Beneficial Soil Bacteria Differently Under Conventional and Organic Farming
Authors: Gebauer Lucie , Breitkreuz Claudia , Heintz-Buschart Anna , Reitz Thomas , Buscot François , Tarkka Mika , Bouffaud Marie-Lara
Published: June 2022

Water deficit tolerance is critical for plant fitness and survival, especially when successive drought events happen. Specific soil microorganisms are however able to improve plant tolerance to stresses, such as those displaying a 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity. Microorganisms adapted to dry conditions can be selected by plants over time because of properties such as sporulation, substrate preference, or cell-wall thickness. However, the complexity and interconnection between abiotic factors, like drought or soil management, and biotic factors, like plant species identity, make it difficult to elucidate the general selection processes of such microorganisms. Using a pot experiment in which wheat and barley were grown on conventional and organic farming soils, we determined the effect of water deficit history on soil microorganisms by comparing single and successive events of water limitation. The analysis showed that water deficit strongly impacts the composition of both the total microbial community (16S rRNA genes) and one of ACC deaminase-positive (acdS+) microorganisms in the rhizosphere. In contrast, successive dry conditions moderately influence the abundance and diversity of both communities compared to a single dry event. We revealed interactive effects of the farming soil type and the water deficit conditioning treatment. Indeed, possibly due to better nutrient status, plants grown on soils from conventional farming showed higher growth and were able to select more adapted microbial taxa. Some of them are already known for their plant-beneficial properties like the Actinobacteria Streptomyces, but interestingly, some Proteobacteria were also enriched after a water deficit history under conventional farming. Our approach allowed us to identify key microbial taxa promoting drought adaptation of cereals, thus improving our understanding of drought effects on plant-microbe interactions.
Microbial Interactions — Underexplored Links Between Public Health Relevant Bacteria and Protozoa in Coastal Environments
Authors: Eriksson Karolina I. A. , Thelaus Johanna , Andersson Agneta , Ahlinder Jon
Published: June 2022

The co-existence of bacteria and protozoa in aquatic environments has led to the evolution of predation defense mechanisms by the bacteria. Some of the predation-resistant bacteria (PRB) are also pathogenic to humans and other mammals. The links between PRB and protozoa in natural aquatic systems are poorly known, but they are important in predicting outbreaks and determining the long-term consequences of a contamination event. To elucidate co-occurrence patterns between PRB (16S rRNA) and bacterivorous protozoa (18S rRNA), we performed a field study in a coastal area in the northern Baltic Sea. Interactions between bacteria and protozoa were explored by using two complementary statistical tools. We found co-occurrence patterns between specific PRB and protozoa, such as Legionella and Ciliophora, and we also found that the interactions are genotype-specific as, for example, Rickettsia. The PRB sequence diversity was larger in bays and freshwater inlets compared to offshore sites, indicating local adaptions. Considering the PRB diversity in the freshwater in combination with the large spring floods in the area, freshwater influxes should be considered a potential source of PRB in the coastal northern Baltic Sea. These findings are relevant for the knowledge of survival and dispersal of potential pathogens in the environment.
A Functional Variant in the Aquaporin-3 Promoter Modulates Its Expression and Correlates With Resistance to Porcine Epidemic Virus Infection in Porcine Intestinal Epithelial Cells
Authors: Wang Haifei , Bi Zhenbin , Dai Kaiyu , Li Pinghua , Huang Ruihua , Wu Shenglong , Bao Wenbin
Published: June 2022

Porcine epidemic diarrhea virus (PEDV) causes a highly contagious intestinal disease in neonatal pigs. Aquaporin-3 (AQP3) plays important roles in maintenance of intestinal barrier function and regulation of immune responses. However, the roles of AQP3 in mediating PEDV infection to host cells and the regulatory mechanisms of AQP3 expression remain poorly understood. Here, we identified one 16 bp (GGGCGGGGTTGCGGGC) insertion mutation in the AQP3 gene promoter in Large White pigs, with the frequencies of 49.3% of heterozygotes and 31.3% of mutant homozygotes. Functional analysis by luciferase activity assay indicated that the insertion mutation results in significant enhancement in AQP3 transcriptional activity (P < 0.01). Mechanistic analysis showed that the inserted sequence adds binding sites for transcription factor CEBPA, which promotes the expression of AQP3. Downregulation of AQP3 by shRNA silencing in porcine intestinal epithelial cells revealed obvious increases in genome copies and viral titers of PEDV. Expression of proinflammatory cytokines (IL-6, IL-8, and IL-18) and interferons (IFN-α and IFN-β) were significantly reduced (P < 0.01) in AQP3 knockdown cells upon PEDV infection. Furthermore, decreased level of ZO-1 protein was also detected in AQP3 knockdown cells in response to PEDV infection. Our findings suggested a previously unknown mechanism linking the effects of promoter genetic variants on the expression of AQP3, revealed the roles of AQP3 in response to PEDV pathogenesis, and indicated the potential associations of the 16 bp insertion mutation with resistance to PEDV infection in porcine intestinal epithelial cells.
Gut Microbial Profile in Asymptomatic Gallstones
Authors: Song Sen-Tao , Cai Ling-Yan , Zeng Xin , Xie Wei-Fen
Published: June 2022

There are few studies on the changes of gut microbiota in patients with gallstones, especially in patients with asymptomatic gallstones, and there are some deficiencies in these studies, for instance, the effects of metabolic factors on gut microbiota are not considered. Here, we selected 30 asymptomatic gallstone patients from the survey population, and 30 controls according to the age and BMI index matching principle. The 16SrDNA technology was used to detect and compare the structural differences in the gut microbiota between the two groups. Compared with healthy controls, the abundance of gut microbiota in patients with gallstones increased significantly, while the microbiota diversity decreased. At the level of phylum, both groups were dominated by Firmicutes, Bacteroides, Proteobacteria, and Actinobacteria. At the genus level, there were 15 species with significant differences in abundance between the two groups. Further subgroup analysis found that only unclassified Lactobacillales showed differences in the intestines of gallstones patients with hypertension, non-alcoholic fatty liver disease, or patients with elevated BMI (≧24). The structure of gut microbiota in patients with gallstones changed significantly, and this might be related to the occurrence of gallstones, rather than metabolic factors such as hypertension, non-alcoholic fatty liver disease, and obesity.
Battling Enteropathogenic Clostridia: Phage Therapy for Clostridioides difficile and Clostridium perfringens
Authors: Venhorst Jennifer , van der Vossen Jos M. B. M. , Agamennone Valeria
Published: June 2022

The pathogenic Clostridioides difficile and Clostridium perfringens are responsible for many health care-associated infections as well as systemic and enteric diseases. Therefore, they represent a major health threat to both humans and animals. Concerns regarding increasing antibiotic resistance (related to C. difficile and C. perfringens) have caused a surge in the pursual of novel strategies that effectively combat pathogenic infections, including those caused by both pathogenic species. The ban on antibiotic growth promoters in the poultry industry has added to the urgency of finding novel antimicrobial therapeutics for C. perfringens. These efforts have resulted in various therapeutics, of which bacteriophages (in short, phages) show much promise, as evidenced by the Eliava Phage Therapy Center in Tbilisi, Georgia (https://eptc.ge/). Bacteriophages are a type of virus that infect bacteria. In this review, the (clinical) impact of clostridium infections in intestinal diseases is recapitulated, followed by an analysis of the current knowledge and applicability of bacteriophages and phage-derived endolysins in this disease indication. Limitations of phage and phage endolysin therapy were identified and require considerations. These include phage stability in the gastrointestinal tract, influence on gut microbiota structure/function, phage resistance development, limited host range for specific pathogenic strains, phage involvement in horizontal gene transfer, and—for phage endolysins—endolysin resistance, -safety, and -immunogenicity. Methods to optimize features of these therapeutic modalities, such as mutagenesis and fusion proteins, are also addressed. The future success of phage and endolysin therapies require reliable clinical trial data for phage(-derived) products. Meanwhile, additional research efforts are essential to expand the potential of exploiting phages and their endolysins for mitigating the severe diseases caused by C. difficile and C. perfringens.
Differences in the Proteomic and Metabolomic Response of Quercus suber and Quercus variabilis During the Early Stages of Phytophthora cinnamomi Infection
Authors: Saiz-Fernández Iñigo , Đorđević Biljana , Kerchev Pavel , Černý Martin , Jung Thomas , Berka Miroslav , Fu Chuen-Hsu , Horta Jung Marília , Brzobohatý Břetislav
Published: June 2022

Phytophthora cinnamomi Rands is a cosmopolite pathogen of woody plants which during the last couple of centuries has spread all over the world from its center of origin in Southeast Asia. In contrast to Chinese cork oak (Quercus variabilis Blume) forests native to Asia, which are generally healthy despite the presence of the pathogen, the populations of Cork oaks (Quercus suber L.) in Europe have been severely decimated by P. cinnamomi. The present study aims at identifying the differences in the early proteomic and metabolomic response of these two tree species that lead to their differences in susceptibility to P. cinnamomi. By using micropropagated clonal plants, we tried to minimize the plant-to-plant differences in the defense response that is maximized by the high intraspecific genetic variability inherent to the Quercus genus. The evolution on the content of Phytophthora proteins in the roots during the first 36 h after inoculation suggests a slower infection process in Q. variabilis plants. These plants displayed a significant decrease in sugars in the roots, together with a downregulation of proteins related to carbon metabolism. In the leaves, the biggest changes in proteomic profiling were observed 16 h after inoculation, and included increased abundance of peroxidases, superoxide dismutases and glutathione S-transferases in Q. variabilis plants, which probably contributed to decrease its susceptibility to P. cinnamomi.
Ecological Drivers of the Soil Microbial Diversity and Composition in Primary Old-Growth Forest and Secondary Woodland in a Subtropical Evergreen Broad-Leaved Forest Biome in the Ailao Mountains, China
Authors: Zeng Qingchao , Lebreton Annie , Man Xiaowu , Jia Liukun , Wang Gengshen , Gong Sai , Buée Marc , Wu Gang , Dai Yucheng , Yang Zhuliang , Martin Francis M.
Published: June 2022

Replacement of primary old-growth forests by secondary woodlands in threatened subtropical biomes drives important changes at the level of the overstory, understory and forest floor, but the impact on belowground microbial biodiversity is yet poorly documented. In the present study, we surveyed by metabarcoding sequencing, the diversity and composition of soil bacteria and fungi in the old-growth forest, dominated by stone oaks (Lithocarpus spp.) and in the secondary Yunnan pine woodland of an iconic site for biodiversity research, the Ailaoshan National Nature Reserve (Ailao Mountains, Yunnan province, China). We assessed the effect of forest replacement and other environmental factors, including soil horizons, soil physicochemical characteristics and seasonality (monsoon vs. dry seasons). We showed that tree composition and variation in soil properties were major drivers for both bacterial and fungal communities, with a significant influence from seasonality. Ectomycorrhizal Operational Taxonomic Units (OTUs) dominated the functional fungal guilds. Species richness and diversity of the bacterial and fungal communities were higher in the pine woodland compared to the primary Lithocarpus forest, although prominent OTUs were different. The slightly lower complexity of the microbiome in the primary forest stands likely resulted from environmental filtering under relatively stable conditions over centuries, when compared to the secondary pine woodlands. In the old-growth forest, we found a higher number of species, but that communities were homogeneously distributed, whereas in the pine woodlands, there is a slightly lower number of species present but the communities are heterogeneously distributed. The present surveys of the bacterial and fungal diversity will serve as references in future studies aiming to assess the impact of the climate change on soil microbial diversity in both old-growth forests and secondary woodlands in Ailaoshan.