bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Concentrations of Circulating Soluble MHC Class I-Related Chain A (sMICA) and sMICB and Modulation of Plasma Membrane MICA Expression: Potential Mechanisms and Correlation With Natural Killer Cell Activity in Systemic Lupus Erythematosus
Authors: Hervier Baptiste , Ribon Matthieu , Tarantino Nadine , Mussard Julie , Breckler Magali , Vieillard Vincent , Amoura Zahir , Steinle Alexander , Klein Reinhild , Kötter Ina , Decker Patrice
Published: May 2021

Systemic lupus erythematosus (SLE) is a severe autoimmune disease of unknown etiology. The major histocompatibility complex (MHC) class I-related chain A (MICA) and B (MICB) are stress-inducible cell surface molecules. MICA and MICB label malfunctioning cells for their recognition by cytotoxic lymphocytes such as natural killer (NK) cells. Alterations in this recognition have been found in SLE. MICA/MICB can be shed from the cell surface, subsequently acting either as a soluble decoy receptor (sMICA/sMICB) or in CD4+ T-cell expansion. Conversely, NK cells are frequently defective in SLE and lower NK cell numbers have been reported in patients with active SLE. However, these cells are also thought to exert regulatory functions and to prevent autoimmunity. We therefore investigated whether, and how, plasma membrane and soluble MICA/B are modulated in SLE and whether they influence NK cell activity, in order to better understand how MICA/B may participate in disease development. We report significantly elevated concentrations of circulating sMICA/B in SLE patients compared with healthy individuals or a control patient group. In SLE patients, sMICA concentrations were significantly higher in patients positive for anti-SSB and anti-RNP autoantibodies. In order to study the mechanism and the potential source of sMICA, we analyzed circulating sMICA concentration in Behcet patients before and after interferon (IFN)-α therapy: no modulation was observed, suggesting that IFN-α is not intrinsically crucial for sMICA release in vivo. We also show that monocytes and neutrophils stimulated in vitro with cytokines or extracellular chromatin up-regulate plasma membrane MICA expression, without releasing sMICA. Importantly, in peripheral blood mononuclear cells from healthy individuals stimulated in vitro by cell-free chromatin, NK cells up-regulate CD69 and CD107 in a monocyte-dependent manner and at least partly via MICA-NKG2D interaction, whereas NK cells were exhausted in SLE patients. In conclusion, sMICA concentrations are elevated in SLE patients, whereas plasma membrane MICA is up-regulated in response to some lupus stimuli and triggers NK cell activation. Those results suggest the requirement for a tight control in vivo and highlight the complex role of the MICA/sMICA system in SLE.
Neonatal T Helper 17 Responses Are Skewed Towards an Immunoregulatory Interleukin-22 Phenotype
Authors: Razzaghian Hamid R. , Sharafian Zohreh , Sharma Ashish A. , Boyce Guilaine K. , Lee Kelsey , Da Silva Rachel , Orban Paul C. , Sekaly Rafick-Pierre , Ross Colin J. , Lavoie Pascal M.
Published: May 2021

Newborns are frequently affected by mucocutaneous candidiasis. Th17 cells essentially limit mucosal invasion by commensal Candida spp. Here, we sought to understand the molecular basis for the developmental lack of Th17 cell responses in circulating blood neonatal T cells. Naive cord blood CD4 T cells stimulated in Th17-differentiating conditions inherently produced high levels of the interleukin-22 immunoregulatory cytokine, particularly in the presence of neonatal antigen-presenting cells. A genome-wide transcriptome analysis comparing neonatal and adult naïve CD4 T cells ex vivo revealed major developmental differences in gene networks regulating Small Drosophila Mothers Against Decapentaplegic (SMAD) and Signal Transducer and Activator of Transcription 3 (STAT3) signaling. These changes were functionally validated by experiments showing that the requirement for TGF-β in human Th17 cell differentiation is age-dependent. Moreover, STAT3 activity was profoundly diminished while overexpression of the STAT3 gene restored Th17 cell differentiation capacity in neonatal T cells. These data reveal that Th17 cell responses are developmentally regulated at the gene expression level in human neonates. These developmental changes may protect newborns against pathological Th17 cell responses, at the same time increasing their susceptibility to mucocutaneous candidiasis.
Naturally Occurring Genetic Alterations in Proximal TCR Signaling and Implications for Cancer Immunotherapy
Authors: Kent Andrew , Longino Natalie V. , Christians Allison , Davila Eduardo
Published: May 2021

T cell-based immunotherapies including genetically engineered T cells, adoptive transfer of tumor-infiltrating lymphocytes, and immune checkpoint blockade highlight the impressive anti-tumor effects of T cells. These successes have provided new hope to many cancer patients with otherwise poor prognoses. However, only a fraction of patients demonstrates durable responses to these forms of therapies and many develop significant immune-mediated toxicity. These heterogeneous clinical responses suggest that underlying nuances in T cell genetics, phenotypes, and activation states likely modulate the therapeutic impact of these approaches. To better characterize known genetic variations that may impact T cell function, we 1) review the function of early T cell receptor-specific signaling mediators, 2) offer a synopsis of known mutations and genetic alterations within the associated molecules, 3) discuss the link between these mutations and human disease and 4) review therapeutic strategies under development or in clinical testing that target each of these molecules for enhancing anti-tumor T cell activity. Finally, we discuss novel engineering approaches that could be designed based on our understanding of the function of these molecules in health and disease.
Crosstalk Between Epithelial Cells, Neurons and Immune Mediators in HSV-1 Skin Infection
Authors: Duarte Luisa F. , Reyes Antonia , Farías Mónica A. , Riedel Claudia A. , Bueno Susan M. , Kalergis Alexis M. , González Pablo A.
Published: May 2021

Herpes simplex virus type 1 (HSV-1) infection is highly prevalent in humans, with approximately two-thirds of the world population living with this virus. However, only a fraction of those carrying HSV-1, which elicits lifelong infections, are symptomatic. HSV-1 mainly causes lesions in the skin and mucosae but reaches the termini of sensory neurons innervating these tissues and travels in a retrograde manner to the neuron cell body where it establishes persistent infection and remains in a latent state until reactivated by different stimuli. When productive reactivations occur, the virus travels back along axons to the primary infection site, where new rounds of replication are initiated in the skin, in recurrent or secondary infections. During this process, new neuron infections occur. Noteworthy, the mechanisms underlying viral reactivations and the exit of latency are somewhat poorly understood and may be regulated by a crosstalk between the infected neurons and components of the immune system. Here, we review and discuss the immune responses that occur at the skin during primary and recurrent infections by HSV-1, as well as at the interphase of latently-infected neurons. Moreover, we discuss the implications of neuronal signals over the priming and migration of immune cells in the context of HSV-1 infection.
RvE1 Impacts the Gingival Inflammatory Infiltrate by Inhibiting the T Cell Response in Experimental Periodontitis
Authors: Alvarez Carla , Abdalla Henrique , Suliman Salwa , Rojas Paola , Wu Yu-Chiao , Almarhoumi Rawan , Huang Ren-Yeong , Galindo Mario , Vernal Rolando , Kantarci Alpdogan
Published: May 2021

Periodontitis is a chronic inflammatory disease associated with the formation of dysbiotic plaque biofilms and characterized by the progressive destruction of the alveolar bone. The transition from health to disease is characterized by a shift in periodontal immune cell composition, from mostly innate (neutrophils) to adaptive (T lymphocytes) immune responses. Resolvin E1 (RvE1) is a specialized pro-resolution mediator (SPMs), produced in response to inflammation, to enhance its resolution. Previous studies have indicated the therapeutic potential of RvE1 in periodontal disease; however, the impact of RvE1 in the microbial-elicited osteoclastogenic immune response remains uncharacterized in vivo. In the present study, we studied the impact of RvE1 on the gingival inflammatory infiltrate formation during periodontitis in a mouse model. First, we characterized the temporal-dependent changes of the main immune cells infiltrating the gingiva by flow cytometry. Then, we evaluated the impact of early or delayed RvE1 administration on the gingival immune infiltration and cervical lymph nodes composition. We observed a consistent inhibitory outcome on T cells -particularly effector T cells- and a protective effect on regulatory T cells (Tregs). Our data further demonstrated the wide range of actions of RvE1, its preventive role in the establishment of the adaptive immune response during inflammation, and bone protective capacity.
Tumor-Associated Antigens (TAAs) for the Serological Diagnosis of Osteosarcoma
Authors: Li Jitian , Qin Bo , Huang Manyu , Ma Yan , Li Dongsheng , Li Wuyin , Guo Zhiping
Published: April 2021

Osteosarcoma (OS) is the most common form of malignant bone tumor found in childhood and adolescence. Although its incidence rate is low among cancers, the prognosis of OS is usually poor. Although some biomarkers, such as p53, have been identified in OS, the association between the biomarkers and clinical outcome is not well understood. Thus, it is necessary to establish a method to identify patients diagnosed with OS at an early stage. It is becoming obvious that anti-tumor-associated antigens (TAAs) autoantibodies (TAAbs) in sera could be used as serological biomarkers in the detection of many different types of cancers. This notion indicates that TAAbs are considered as immunological “sentinels” associated with tumorigenesis underlying molecular events. It provides new insights into the molecular and cellular biology of the differential diagnosis of cancers. What’s more, it is reported that a customized TAA array could significantly increase the sensitivity/specificity. TAA arrays also have great application prospects in detecting cancer at an early stage, monitoring cancer progression, discovering new therapeutic targets, and designing personalized treatment. In this review, we provide an overview of the TAAs identified in OS as well as the possibility that TAAs and TAAbs system be used as biomarkers in the immunodiagnosis and prognosis of OS.
Listeria monocytogenes Establishes Commensalism in Germ-Free Mice Through the Reversible Downregulation of Virulence Gene Expression
Authors: Cho Kyungjin , Spasova Darina , Hong Sung-Wook , O Eunju , Surh Charles D. , Im Sin-Hyeog , Kim Kwang Soon
Published: May 2021

The intestine harbors a complex community of bacterial species collectively known as commensal microbiota. Specific species of resident bacteria, as known as pathobiont, have pathogenic potential and can induce apparent damage to the host and intestinal inflammation in a certain condition. However, the host immune factors that permit its commensalism under steady state conditions are not clearly understood. Here, we studied the gut fitness of Listeria monocytogenes by using germ-free (GF) mice orally infected with this food-borne pathogen. L. monocytogenes persistently exists in the gut of GF mice without inducing chronic immunopathology. L. monocytogenes at the late phase of infection is not capable of infiltrating through the intestinal barrier. L. monocytogenes established the commensalism through the reversible down regulation of virulence gene expression. CD8+ T cells were found to be sufficient for the commensalism of L. monocytogenes. CD8+ T cells responding to L. monocytogenes contributed to the down-regulation of virulence gene expression. Our data provide important insights into the host-microbe interaction and have implications for developing therapeutics against immune disorders induced by intestinal pathogens or pathobionts.
False Positive Results in SARS-CoV-2 Serological Tests for Samples From Patients With Chronic Inflammatory Diseases
Authors: Kharlamova Nastya , Dunn Nicky , Bedri Sahl K. , Jerling Svante , Almgren Malin , Faustini Francesca , Gunnarsson Iva , Rönnelid Johan , Pullerits Rille , Gjertsson Inger , Lundberg Karin , Månberg Anna , Pin Elisa , Nilsson Peter , Hober Sophia , Fink Katharina , Fogdell-Hahn Anna
Published: May 2021

Patients with chronic inflammatory diseases are often treated with immunosuppressants and therefore are of particular concern during the SARS-CoV-2 pandemic. Serological tests will improve our understanding of the infection and immunity in this population, unless they tests give false positive results. The aim of this study was to evaluate the specificity of SARS-Cov-2 serological assays using samples from patients with chronic inflammatory diseases collected prior to April 2019, thus defined as negative. Samples from patients with multiple sclerosis (MS, n=10), rheumatoid arthritis (RA, n=47) with or without rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (anti-CCP2) and systemic lupus erythematosus (SLE, n=10) with or without RF, were analyzed for SARS-CoV-2 antibodies using 17 commercially available lateral flow assays (LFA), two ELISA kits and one in-house developed IgG multiplex bead-based assay. Six LFA and the in-house validated IgG assay correctly produced negative results for all samples. However, the majority of assays (n=13), gave false positive signal for samples from patients with RA and SLE. This was most notable in samples from RF positive RA patients. No false positive samples were detected in any assay using samples from patients with MS. Poor specificity of commercial serological assays could possibly be, at least partly, due to interfering antibodies in samples from patients with chronic inflammatory diseases. For these patients, the risk of false positivity should be considered when interpreting results of the SARS-CoV-2 serological assays.
Differentiation and Regulation of TH Cells: A Balancing Act for Cancer Immunotherapy
Authors: Basu Amrita , Ramamoorthi Ganesan , Albert Gabriella , Gallen Corey , Beyer Amber , Snyder Colin , Koski Gary , Disis Mary L. , Czerniecki Brian J. , Kodumudi Krithika
Published: May 2021

Current success of immunotherapy in cancer has drawn attention to the subsets of THcells in the tumor which are critical for activation of anti-tumor response either directly by themselves or by stimulating cytotoxic T cell activity. However, presence of immunosuppressive pro-tumorigenic THsubsets in the tumor milieu further contributes to the complexity of regulation of THcell-mediated immune response. In this review, we present an overview of the multifaceted positive and negative effects of THcells, with an emphasis on regulation of different THcell subtypes by various immune cells, and how a delicate balance of contradictory signals can influence overall success of cancer immunotherapy. We focus on the regulatory network that encompasses dendritic cell-induced activation of CD4+TH1 cells and subsequent priming of CD8+cytotoxic T cells, along with intersecting anti-inflammatory and pro-tumorigenic TH2 cell activity. We further discuss how other tumor infiltrating immune cells such as immunostimulatory TH9 and Tfhcells, immunosuppressive Tregcells, and the duality of TH17 function contribute to tip the balance of anti- vs pro-tumorigenic THresponses in the tumor. We highlight the developing knowledge of CD4+TH1 immune response against neoantigens/oncodrivers, impact of current immunotherapy strategies on CD4+TH1 immunity, and how opposing action of THcell subtypes can be explored further to amplify immunotherapy success in patients. Understanding the nuances of CD4+THcells regulation and the molecular framework undergirding the balancing act between anti- vs pro-tumorigenic THsubtypes is critical for rational designing of immunotherapies that can bypass therapeutic escape to maximize the potential of immunotherapy.
The Role of Semaphorins and Their Receptors in Innate Immune Responses and Clinical Diseases of Acute Inflammation
Authors: Kanth Shreya M. , Gairhe Salina , Torabi-Parizi Parizad
Published: May 2021

Semaphorins are a group of proteins that have been studied extensively for their critical function in neuronal development. They have been shown to regulate airway development, tumorigenesis, autoimmune diseases, and the adaptive immune response. Notably, emerging literature describes the role of immunoregulatory semaphorins and their receptors, plexins and neuropilins, as modulators of innate immunity and diseases defined by acute injury to the kidneys, abdomen, heart and lungs. In this review we discuss the pathogenic functions of semaphorins in clinical conditions of acute inflammation, including sepsis and acute lung injury, with a focus on regulation of the innate immune response as well as potential future therapeutic targeting.
Insulin Signaling in Arthritis
Authors: Tripolino Cesare , Ciaffi Jacopo , Pucino Valentina , Ruscitti Piero , van Leeuwen Nina , Borghi Claudio , Giacomelli Roberto , Meliconi Riccardo , Ursini Francesco
Published: April 2021

Inflammatory arthritis is burdened by an increased risk of metabolic disorders. Cytokines and other mediators in inflammatory diseases lead to insulin resistance, diabetes and hyperlipidemia. Accumulating evidence in the field of immunometabolism suggests that the cause-effect relationship between arthritis and metabolic abnormalities might be bidirectional. Indeed, the immune response can be modulated by various factors such as environmental agents, bacterial products and hormones. Insulin is produced by pancreatic cells and regulates glucose, fat metabolism and cell growth. The action of insulin is mediated through the insulin receptor (IR), localized on the cellular membrane of hepatocytes, myocytes and adipocytes but also on the surface of T cells, macrophages, and dendritic cells. In murine models, the absence of IR in T-cells coincided with reduced cytokine production, proliferation, and migration. In macrophages, defective insulin signaling resulted in enhanced glycolysis affecting the responses to pathogens. In this review, we focalize on the bidirectional cause-effect relationship between impaired insulin signaling and arthritis analyzing how insulin signaling may be involved in the aberrant immune response implicated in arthritis and how inflammatory mediators affect insulin signaling. Finally, the effect of glucose-lowering agents on arthritis was summarized.
Regulation of Tissue Immune Responses by Local Glucocorticoids at Epithelial Barriers and Their Impact on Interorgan Crosstalk
Authors: Merk Verena M. , Phan Truong San , Brunner Thomas
Published: May 2021

The anti-inflammatory role of extra-adrenal glucocorticoid (GC) synthesis at epithelial barriers is of increasing interest with regard to the search for alternatives to synthetic corticosteroids in the therapy of inflammatory disorders. Despite being very effective in many situations the use of synthetic corticosteroids is often controversial, as exemplified in the treatment of influenza patients and only recently in the current COVID-19 pandemic. Exploring the regulatory capacity of locally produced GCs in balancing immune responses in barrier tissues and in pathogenic disorders that lead to symptoms in multiple organs, could provide new perspectives for drug development. Intestine, skin and lung represent the first contact zones between potentially harmful pathogens or substances and the body, and are therefore important sites of immunoregulatory mechanisms. Here, we review the role of locally produced GCs in the regulation of type 2 immune responses, like asthma, atopic dermatitis and ulcerative colitis, as well as type 1 and type 3 infectious, inflammatory and autoimmune diseases, like influenza infection, psoriasis and Crohn’s disease. In particular, we focus on the role of locally produced GCs in the interorgan communication, referred to as gut-skin axis, gut-lung axis or lung-skin axis, all of which are interconnected in the pathogenic crosstalk atopic march.
Immune Response to COVID-19 During Pregnancy
Authors: Chen Ge , Liao Qiuyue , Ai Jihui , Yang Bin , Bai Hualin , Chen Jing , Liu Fengyuan , Cao Yang , Liu Haiyi , Li Kezhen
Published: May 2021

Pregnant women are generally more susceptible to viral infection. Although the impact of SARS-CoV-2 on pregnant women remains to be determined, evidence indicates that risks of adverse clinical outcomes are similar in pregnancy to the general population. Here we analyzed clinical symptoms and outcomes of 20 pregnant and 299 reproductive-aged non-pregnant female COVID-19 patients who were hospitalized during the same period. Laboratory measurements were compared among mild cases and healthy pregnant women. Our study found that pregnant patients showed enhanced innate immune response evident by higher neutrophils and C-reactive protein. Cytokines, chemokines, and growth factors (CCGFs) profiles from 11 pregnant and 4 non-pregnant COVID-19 patients and 10 healthy pregnant female patients, and lymphocyte subsets analysis of 7 pregnant patients and 19 non-pregnant patients, indicate suppressed cytokine storm and potential enhanced CD8+ T cell and NK cell activity in pregnant patients with COVID-19, which may be essential in contributing to the unique anti-SARS-CoV-2 response in pregnancy.
3D Scanning as a Tool to Measure Growth Rates of Live Coral Microfragments Used for Coral Reef Restoration
Authors: Koch Hanna R. , Wallace Bailey , DeMerlis Allyson , Clark Abigail S. , Nowicki Robert J.
Published: April 2021

Rapid and widespread declines in coral health and abundance have driven increased investments in coral reef restoration interventions to jumpstart population recovery. Microfragmentation, an asexual propagation technique, is used to produce large numbers of corals for research and restoration. As part of resilience-based restoration, coral microfragments of different genotypes and species are exposed to various stressors to identify candidates for propagation. Growth rate is one of several important fitness-related traits commonly used in candidate selection, and being able to rapidly and accurately quantify growth rates of different genotypes is ideal for high-throughput stress tests. Additionally, it is crucial, as coral restoration becomes more commonplace, to establish practical guidelines and standardized methods of data collection that can be used across independent groups. Herein, we developed a streamlined workflow for growth rate quantification of live microfragmented corals using a structured-light 3D scanner to assess surface area (SA) measurements of live tissue over time. We then compared novel 3D and traditional 2D approaches to quantifying microfragment growth rates and assessed factors such as accuracy and speed. Compared to a more conventional 2D approach based on photography and ImageJ analysis, the 3D approach had comparable reliability, greater accuracy regarding absolute SA quantification, high repeatability, and low variability between scans. However, the 2D approach accurately measured growth and proved to be faster and cheaper, factors not trivial when attempting to upscale for restoration efforts. Nevertheless, the 3D approach has greater capacity for standardization across dissimilar studies, making it a better tool for restoration practitioners striving for consistent and comparable data across users, as well as for those conducting networked experiments, meta-analyses, and syntheses. Furthermore, 3D scanning has the capacity to provide more accurate surface area (SA) measurements for rugose, mounding, or complex colony shapes. This is the first protocol developed for using structured-light 3D scanning as a tool to measure growth rates of live microfragments. While each method has its advantages and disadvantages, disadvantages to a 3D approach based on speed and cost may diminish with time as interest and usage increase. As a resource for coral restoration practitioners and researchers, we provide a detailed 3D scanning protocol herein and discuss its potential limitations, applications, and future directions.
Exploring the Pacific Arctic Seasonal Ice Zone With Saildrone USVs
Authors: Chiodi Andrew M. , Zhang Chidong , Cokelet Edward D. , Yang Qiong , Mordy Calvin W. , Gentemann Chelle L. , Cross Jessica N. , Lawrence-Slavas Noah , Meinig Christian , Steele Michael , Harrison Don E. , Stabeno Phyllis J. , Tabisola Heather M. , Zhang Dongxiao , Burger Eugene F. , O’Brien Kevin M. , Wang Muyin
Published: May 2021

More high-quality, in situ observations of essential marine variables are needed over the seasonal ice zone to better understand Arctic (or Antarctic) weather, climate, and ecosystems. To better assess the potential for arrays of uncrewed surface vehicles (USVs) to provide such observations, five wind-driven and solar-powered saildrones were sailed into the Chukchi and Beaufort Seas following the 2019 seasonal retreat of sea ice. They were equipped to observe the surface oceanic and atmospheric variables required to estimate air-sea fluxes of heat, momentum and carbon dioxide. Some of these variables were made available to weather forecast centers in real time. Our objective here is to analyze the effectiveness of existing remote ice navigation products and highlight the challenges and opportunities for improving remote ice navigation strategies with USVs. We examine the sources of navigational sea-ice distribution information based on post-mission tabulation of the sea-ice conditions encountered by the vehicles. The satellite-based ice-concentration analyses consulted during the mission exhibited large disagreements when the sea ice was retreating fastest (e.g., the 10% concentration contours differed between analyses by up to ∼175 km). Attempts to use saildrone observations to detect the ice edge revealed that in situ temperature and salinity measurements varied sufficiently in ice bands and open water that it is difficult to use these variables alone as a reliable ice-edge indicator. Devising robust strategies for remote ice zone navigation may depend on developing the capability to recognize sea ice and initiate navigational maneuvers with cameras and processing capability onboard the vehicles.
Geographical Variation in Phenotypic Plasticity of Intertidal Sister Limpet’s Species Under Ocean Acidification Scenarios
Authors: Lardies Marco Antonio , Caballero Paz , Duarte Cristián , Poupin María Josefina
Published: May 2021

Ocean Acidification (OA) can have pervasive effects in calcifying marine organisms, and a better understanding of how different populations respond at the physiological and evolutionary level could help to model the impacts of global change in marine ecosystems. Due to its natural geography and oceanographic processes, the Chilean coast provides a natural laboratory where benthic organisms are frequently exposed to diverse projected OA scenarios. The goal of this study was to assess whether a population of mollusks thriving in a more variable environment (Talcaruca) would present higher phenotypic plasticity in physiological and morphological traits in response to differentpCO2when compared to a population of the same species from a more stable environment (Los Molles). To achieve this, two benthic limpets (Scurria zebrinaandScurria viridula) inhabiting these two contrasting localities were exposed to ocean acidification experimental conditions representing the currentpCO2in the Chilean coast (500 μatm) and the levels predicted for the year 2100 in upwelling zones (1500 (μatm). Our results show that the responses to OA are species-specific, even in this related species. Interestingly, S. viridula showed better performance under OA than S. zebrina (i.e., similar sizes and carbonate content in individuals from both populations; lower effects of acidification on the growth rate combined with a reduction of metabolism at higherpCO2). Remarkably, these characteristics could explain this species’ success in overstepping the biogeographical break in the area of Talcaruca, which S. zebrina cannot achieve. Besides, the results show that the habitat factor has a strong influence on some traits. For instance, individuals from Talcaruca presented a higher growth rate plasticity index and lower shell dissolution rates in acidified conditions than those from Los Molles. These results show that limpets from the variable environment tend to display higher plasticity, buffering the physiological effects of OA compared with limpets from the more stable environment. Taken together, these findings highlight the key role of geographic variation in phenotypic plasticity to determine the vulnerability of calcifying organisms to future scenarios of OA.
PtP38 May Increase the Immune Ability of Portunus trituberculatus Stimulated by LPS Imitating a Gram-Negative Bacterial Infection
Authors: Lu Cheng-Peng , Wei Chao-Guang , Zhu Jun-Quan , Tang Dao-Jun , Wang Chun-Lin , Hou Cong-Cong
Published: May 2021

The P38 mitogen-activated protein kinase (MAPK) signal transduction pathway is widespread in organisms and plays important roles in immune activities. The infection mechanism of environmental gram-negative bacteria on crustaceans is an important scientific problem. In this study, the cDNA full-length sequence ofPortunus trituberculatusP38 (PtP38) was cloned and its structure was analyzed by bioinformatics methods. To study the function of the PtP38 gene after a Gram-negative bacterial infection, we injectedP. trituberculatuswith LPS to activate the immune response instead of directly infecting with Gram-negative bacteria. With LPS stimulation, the expression of the PtP38 gene in different tissues increased significantly. At the same time, the expression of immune-related genes (ALF and crustin) in the hepatopancreas, activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and inducible nitric oxide synthase (iNOS) enzymes], and expression of apoptosis-related genes (caspase2 and caspase3) were increased significantly. To further conform the function of PtP38 in the immune response, we injectedP. trituberculatuswith P38 inhibitor and subsequently injected with LPS. The results showed that the expression of immune-related genes was inhibited, the activity of antioxidant enzymes was decreased, and the expression of apoptosis-related genes were inhibited. Thus, we speculated that PtP38 may increase the immune ability by improving the expression of antimicrobial peptides, increasing the activity of oxidative stress-related enzymes, and promoting cell apoptosis in infectedP. trituberculatus. This study also laid the foundation for further study of the P38 MAPK signaling pathway and immune mechanism ofP. trituberculatus.
Scale-Specific Patterns of the Production of the Charophyte Chara aspera in the Brackish Baltic Sea: Linking Individual and Community Production and Biomass Growth
Authors: Kotta Jonne , Torn Kaire , Paalme Tiina , Rätsep Merli , Kaljurand Kaire , Teeveer Martin , Kotta Ilmar
Published: April 2021

An understanding of the nature of scale-dependence in macroalgal production and to quantify how primary production is incorporated into autotrophic biomass requires an assessment of primary production at multiple scales. In this study we experimentally estimated seasonal variability in individual photosynthesis, community production and growth in biomass of the charophyteChara asperain the Baltic Sea together with the key environmental variables known to regulate the production of macroalgae. The experiments suggested that the production and growth ofC. asperawas defined largely by light and temperature at all studied scales. However, the algal production at the same light levels was systematically lower at the community than an individual level, suggesting the importance of shelf-shading and below-ground processes in natural plant assemblages. Moreover, the observation scale also defined response types between the environment, plant production and growth. This implies that the patterns of variability of the production and growth of macrophytes should always be interpreted in the context of scale and any multiscale model development should involve experimental validation at all important scales.
A Flow Cytometry-Based Serological Assay to Detect Visceral Leishmaniasis in HIV-Infected Patients
Authors: da Silva Elis D. , de Oliveira Beatriz C. , Pereira Allana M. de S. , Guedes Diego L. , de Melo Neto Osvaldo P. , Costa Carlos H. N. , de Medeiros Zulma M. , Pereira Valéria R. A.
Published: April 2021

Visceral Leishmaniasis (VL) is a severe parasitic disease that has emerged as an important opportunistic condition in HIV-infected patients and whose control is impaired by inaccurate identification. This is mainly due to the serological tests used for VL having a reduced performance in cases of VL-HIV coinfection due to a low humoral response. In this situation, however, a positive test has even greater diagnostic value when combined with the clinical status. This study aimed to evaluate the application and performance of flow cytometry to detect anti-Leishmania infantumantibodies in HIV-infected patients. Sera from VL/HIV coinfected patients, characterized using “gold standard” techniques, were compared with sera from healthy controls plus sera from HIV-infected individuals. The flow cytometry results were expressed as levels of IgG reactivity, based on the percentage of positive fluorescent parasites (PPFP). A ROC curve analysis of a serum titration indicated a PPFP of 1.26% as being the cutoff point to segregate positive and negative results. At the 1:2,048 dilution, with 89% sensitivity and 83% specificity, flow cytometry showed greater sensitivity in relation to the serological tests evaluated. Futhermore, flow cytometry was the only assay that positively identified all VL-HIV patients with quantified HIV load. Together, these findings suggest that flow cytometry may be used as an alternative serological approach for VL identification and as a tool to characterize the humoral response againstLeishmania infantumin HIV-infected patients.
Treatment With Vasopressor Agents for Cardiovascular Shock Patients With Poor Renal Function; Results From the Japanese Circulation Society Cardiovascular Shock Registry
Authors: Yagi Tsukasa , Nagao Ken , Tachibana Eizo , Yonemoto Naohiro , Sakamoto Kazuo , Ueki Yasushi , Imamura Hiroshi , Miyamoto Takamichi , Takahashi Hiroshi , Hanada Hiroyuki , Chiba Nobutaka , Tani Shigemasa , Matsumoto Naoya , Okumura Yasuo
Published: May 2021

According to the guidelines for cardiogenic shock, norepinephrine is associated with fewer arrhythmias than dopamine and may be the better first-line vasopressor agent. This study aimed to evaluate the utility of norepinephrine vs. dopamine as first-line vasopressor agent for cardiovascular shock depending on the presence and severity of renal dysfunction at hospitalization. This was a secondary analysis of the prospective, multicenter Japanese Circulation Society Cardiovascular Shock Registry (JCS Shock Registry) conducted between 2012 and 2014, which included patients with shock complicating emergency cardiovascular disease at hospital arrival. The analysis included 240 adult patients treated with norepinephrine alone (n = 98) or dopamine alone (n = 142) as the first-line vasopressor agent. Primary endpoint was mortality at 30 days after hospital arrival. The two groups had similar baseline characteristics, including estimated glomerular filtration rate (eGFR), and similar 30-day mortality rates. The analysis of the relationship between 30-day mortality rate after hospital arrival and vasopressor agent used in patients categorized according to the eGFR-based chronic kidney disease classification revealed that norepinephrine as the first-line vasopressor agent might be associated with better prognosis of cardiovascular shock in patients with mildly compromised renal function at admission (0.0 vs. 22.6%; P = 0.010) and that dopamine as the first-line vasopressor agent might be beneficial for cardiovascular shock in patients with severely compromised renal function [odds ratio; 0.22 (95% confidence interval 0.05–0.88; P = 0.032)]. Choice of first-line vasopressor agent should be based on renal function at hospital arrival for patients in cardiovascular shock.

Clinical Trial Registration:http://www.umin.ac.jp/ctr/, Unique identifier: 000008441.
Coagulopathy Induced by Veno-Arterial Extracorporeal Membrane Oxygenation Is Associated With a Poor Outcome in Patients With Out-of-Hospital Cardiac Arrest
Authors: Tsuchida Takumi , Wada Takeshi , Gando Satoshi
Published: April 2021

Background: In recent years, the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiopulmonary arrest who do not respond to conventional resuscitation, has increased. However, despite the development of VA-ECMO, the outcomes of resuscitated patients remain poor. The poor prognosis may be attributed to deterioration owing to the post-cardiac arrest syndrome (PCAS); this includes the systemic inflammatory response and coagulation activation caused by the extracorporeal circulation (VA-ECMO circuit) itself. This study aimed to evaluate the coagulofibrinolytic changes caused by VA-ECMO and to identify predictive factors of poor prognosis.

Methods: We analyzed 151 cases of PCAS with witnessed cardiac arrest. As biomarkers, platelet counts, prothrombin time ratio, fibrin/fibrinogen degradation products, fibrinogen, antithrombin, and lactate were recorded from blood samples from the time of delivery to the third day of hospitalization. The maximum (max) and minimum (min) values of each factor during the study period were calculated. To evaluate the impact of VA-ECMO on patients with PCAS, we performed propensity score matching between the patients who received and did not receive VA-ECMO. Sub-analysis was performed for the group with VA-ECMO.

Results: There were significant differences in all baseline characteristics and demographics except the time from detection to hospital arrival, percentage of cardiopulmonary resuscitations (CPR) by witnesses, and the initial rhythm between the groups. Propensity score matching adjusted for prehospital factors demonstrated that the patients who received VA-ECMO developed significantly severe coagulation disorders. In a sub-analysis, significant differences were noted in the prothrombin time ratio min, fibrinogen max, antithrombin max, and lactate min between survivors and non-survivors. In particular, the prothrombin time ratio min and antithrombin max were strongly correlated with poor outcome.

Conclusion: In the present study, significant coagulopathy was observed in patients who received VA-ECMO for CPR. In particular, in patients receiving VA-ECMO, the minimum prothrombin time ratio and maximum antithrombin by day 3 of hospitalization were strongly correlated with poor outcomes. These results suggest that VA-ECMO-induced coagulopathy can be a promising therapeutic target for patients resuscitated by VA-ECMO.
Bacteriophages Are Good Estimators of Human Viruses Present in Water
Authors: Ballesté Elisenda , Blanch Anicet R. , Mendez Javier , Sala-Comorera Laura , Maunula Leena , Monteiro Silvia , Farnleitner Andreas H. , Tiehm Andreas , Jofre Joan , García-Aljaro Cristina
Published: May 2021

The detection of fecal viral pathogens in water is hampered by their great variety and complex analysis. As traditional bacterial indicators are poor viral indicators, there is a need for alternative methods, such as the use of somatic coliphages, which have been included in water safety regulations in recent years. Some researchers have also recommended the use of reference viral pathogens such as noroviruses or other enteric viruses to improve the prediction of fecal viral pollution of human origin. In this work, phages previously tested in microbial source tracking studies were compared with norovirus and adenovirus for their suitability as indicators of human fecal viruses. The phages, namely those infecting human-associated Bacteroides thetaiotaomicron strain GA17 (GA17PH) and porcine-associated Bacteroides strain PG76 (PGPH), and the human-associated crAssphage marker (crAssPH), were evaluated in sewage samples and fecal mixtures obtained from different animals in five European countries, along with norovirus GI + GII (NoV) and human adenovirus (HAdV). GA17PH had an overall sensitivity of ≥83% and the highest specificity (>88%) for human pollution source detection. crAssPH showed the highest sensitivity (100%) and specificity (100%) in northern European countries but a much lower specificity in Spain and Portugal (10 and 30%, respectively), being detected in animal wastewater samples with a high concentration of fecal indicators. The correlations between GA17PH, crAssPH, or the sum of both (BACPH) and HAdV or NoV were higher than between the two human viruses, indicating that bacteriophages are feasible indicators of human viral pathogens of fecal origin and constitute a promising, easy to use and affordable alternative to human viruses for routine water safety monitoring.
Genotypic Characterization of Clinical Klebsiella spp. Isolates Collected From Patients With Suspected Community-Onset Sepsis, Sweden
Authors: Saxenborn Patricia , Baxter John , Tilevik Andreas , Fagerlind Magnus , Dyrkell Fredrik , Pernestig Anna-Karin , Enroth Helena , Tilevik Diana
Published: April 2021

Klebsiella is a genus of Gram-negative bacteria known to be opportunistic pathogens that may cause a variety of infections in humans. Highly drug-resistant Klebsiella species, especially K. pneumoniae, have emerged rapidly and are becoming a major concern in clinical management. Although K. pneumoniae is considered the most important pathogen within the genus, the true clinical significance of the other species is likely underrecognized due to the inability of conventional microbiological methods to distinguish between the species leading to high rates of misidentification. Bacterial whole-genome sequencing (WGS) enables precise species identification and characterization that other technologies do not allow. Herein, we have characterized the diversity and traits of Klebsiella spp. in community-onset infections by WGS of clinical isolates (n = 105) collected during a prospective sepsis study in Sweden. The sequencing revealed that 32 of the 82 isolates (39.0%) initially identified as K. pneumoniae with routine microbiological methods based on cultures followed by matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF MS) had been misidentified. Of these, 23 were identified as Klebsiella variicola and nine as other members of the K. pneumoniae complex. Comparisons of the number of resistance genes showed that significantly fewer resistance genes were detected in Klebsiella oxytoca compared to K. pneumoniae and K. variicola (both values of p < 0.001). Moreover, a high proportion of the isolates within the K. pneumoniae complex were predicted to be genotypically multidrug-resistant (MDR; 79/84, 94.0%) in contrast to K. oxytoca (3/16, 18.8%) and Klebsiella michiganensis (0/4, 0.0%). All isolates predicted as genotypically MDR were found to harbor the combination of β-lactam, fosfomycin, and quinolone resistance markers. Multi-locus sequence typing (MLST) revealed a high diversity of sequence types among the Klebsiella spp. with ST14 (10.0%) and ST5429 (10.0%) as the most prevalent ones for K. pneumoniae, ST146 for K. variicola (12.0%), and ST176 for K. oxytoca (25.0%). In conclusion, the results from this study highlight the importance of using high-resolution genotypic methods for identification and characterization of clinical Klebsiella spp. isolates. Our findings indicate that infections caused by other members of the K. pneumoniae complex than K. pneumoniae are a more common clinical problem than previously described, mainly due to high rates of misidentifications.
A Virus Infecting Hibiscus rosa-sinensis Represents an Evolutionary Link Between Cileviruses and Higreviruses
Authors: Olmedo-Velarde Alejandro , Hu John , Melzer Michael J.
Published: May 2021

Hibiscus (Hibiscus spp.) are popular ornamental and landscape plants in Hawaii which are susceptible to foliar diseases caused by viruses belonging to the genera Cilevirus and Higrevirus (family Kitaviridae). In this study, a virus infecting H. rosa-sinensis plants displaying foliar symptoms consistent with infection by a kitavirus, including yellow chlorotic blotches with a green perimeter, was characterized. The genome consisted of two RNAs 8.4 and 4.4 kb in length, and was organized most similarly to cileviruses, but with important distinctions. These included the location of the p29 homolog as the 3′-terminal open reading frame (ORF) of RNA2 instead of its typical locus at the 3′-end of RNA1; the absence of a p15 homolog on RNA2 and the adjacent intergenic region which also harbors small putative ORFs of unknown function; and the presence of an ORF encoding a 10 kDa protein at the 3′-terminal end of RNA1 that was also found to be present in the hibiscus green spot virus 2 genome. Spherical particles approximately 55–65 nm in diameter were observed in infected leaf tissue, and viral RNA was detected by reverse-transcription PCR in individual mites collected from symptomatic plants tentatively identified as Brevipalpus yothersi. Although phylogenetic analyses placed this virus between the higrevirus and cilevirus clades, we propose the tentative taxonomic placement of this virus, designated hibiscus yellow blotch virus (HYBV), within the genus Cilevirus.
Infant-Associated Bifidobacterial β-Galactosidases and Their Ability to Synthesize Galacto-Oligosaccharides
Authors: Ambrogi Valentina , Bottacini Francesca , O’Callaghan John , Casey Eoghan , van Breen Justin , Schoemaker Barry , Cao Linqiu , Kuipers Bas , O’Connell Motherway Mary , Schoterman Margriet , van Sinderen Douwe
Published: May 2021

Galacto-oligosaccharides (GOS) represent non-digestible glycans that are commercially produced by transgalactosylation of lactose, and that are widely used as functional food ingredients in prebiotic formulations, in particular in infant nutrition. GOS consumption has been reported to enhance growth of specific bacteria in the gut, in particular bifidobacteria, thereby supporting a balanced gut microbiota. In a previous study, we assessed the hydrolytic activity and substrate specificity of seventeen predicted β-galactosidases encoded by various species and strains of infant-associated bifidobacteria. In the current study, we further characterized seven out of these seventeen bifidobacterial β-galactosidases in terms of their kinetics, enzyme stability and oligomeric state. Accordingly, we established whether these β-galactosidases are capable of synthesizing GOS via enzymatic transgalactosylation employing lactose as the feed substrate. Our findings show that the seven selected enzymes all possess such transgalactosylation activity, though they appear to differ in their efficiency by which they perform this reaction. From chromatography analysis, it seems that these enzymes generate two distinct GOS mixtures: GOS with a relatively short or long degree of polymerization profile. These findings may be the stepping stone for further studies aimed at synthesizing new GOS variants with novel and/or enhanced prebiotic activities and potential for industrial applications.