bluuebunny/crossref_metadata_2025 huggingface dataset:
Shedding of Trypanosoma cruzi Surface Molecules That Regulate Host Cell Invasion Involves Phospholipase C and Increases Upon Sterol Depletion
Authors: Loch Leonardo , Onofre Thiago Souza , Rodrigues João Paulo Ferreira , Yoshida Nobuko
Published: October 2021

Metacyclic trypomastigote (MT) forms of Trypanosoma cruzi have been shown to release into medium gp82 and gp90, the stage-specific surface molecules that regulate host cell invasion, either in vesicles or in soluble form. Here, we found that during interaction of poorly invasive G strain with the host cell, gp82 and gp90 were released in vesicle-like forms, whereas no such release by highly invasive CL strain was observed. Shedding of vesicles of varying sizes by CL and G strains was visualized by scanning electron microscopy, and the protein profile of conditioned medium (CM) of the two strains was similar, but the content of gp82 and gp90 differed, with both molecules being detected in G strain as bands of high intensity in Western blotting, whereas in CL strain, they were barely detectable. Confocal images revealed a distinct distribution of gp82 and gp90 on MT surface of CL and G strains. In cell invasion assays, addition of G strain CM resulted in decreased CL strain internalization. Depletion of gp82 in G strain CM, by treatment with specific mAb-coupled magnetic beads, increased its inhibitory effect on CL strain invasion, in contrast to CM depleted in gp90. The effect of cholesterol-depleting drug methyl-β-cyclodextrin (MβCD) on gp82 and gp90 release by MTs was also examined. G strain MTs, untreated or treated with MβCD, were incubated in serum-containing medium or in nutrient-depleted PBS++, and the CM generated under these conditions was analyzed by Western blotting. In PBS++, gp82 and gp90 were released at lower levels by untreated MTs, as compared with MβCD-treated parasites. CM from untreated and MβCD-treated G strain, generated in PBS++, inhibited CL strain internalization. Treatment of CL strain MTs with MβCD resulted in increased gp82 and gp90 shedding and in decreased host cell invasion. The involvement of phospholipase C (PLC) on gp82 and gp90 shedding was also investigated. The CM from G strain MTs pretreated with specific PLC inhibitor contained lower levels of gp82 and gp90, as compared with untreated parasites. Our results contribute to shed light on the mechanism by which T. cruzi releases surface molecules implicated in host cell invasion.
PRD-Containing Virulence Regulators (PCVRs) in Pathogenic Bacteria
Authors: Rom Joseph S. , Hart Meaghan T. , McIver Kevin S.
Published: October 2021

Bacterial pathogens rely on a complex network of regulatory proteins to adapt to hostile and nutrient-limiting host environments. The phosphoenolpyruvate phosphotransferase system (PTS) is a conserved pathway in bacteria that couples transport of sugars with phosphorylation to monitor host carbohydrate availability. A family of structurally homologous PTS-regulatory-domain-containing virulence regulators (PCVRs) has been recognized in divergent bacterial pathogens, including Streptococcus pyogenes Mga and Bacillus anthracis AtxA. These paradigm PCVRs undergo phosphorylation, potentially via the PTS, which impacts their dimerization and their activity. Recent work with predicted PCVRs from Streptococcus pneumoniae (MgaSpn) and Enterococcus faecalis (MafR) suggest they interact with DNA like nucleoid-associating proteins. Yet, Mga binds to promoter sequences as a homo-dimeric transcription factor, suggesting a bi-modal interaction with DNA. High-resolution crystal structures of 3 PCVRs have validated the domain structure, but also raised additional questions such as how ubiquitous are PCVRs, is PTS-mediated histidine phosphorylation via potential PCVRs widespread, do specific sugars signal through PCVRs, and do PCVRs interact with DNA both as transcription factors and nucleoid-associating proteins? Here, we will review known and putative PCVRs based on key domain and functional characteristics and consider their roles as both transcription factors and possibly chromatin-structuring proteins.
Galectin-3 Mediates Thrombin-Induced Vascular Smooth Muscle Cell Migration
Authors: Tian Lei , Huang Chun-Kai , Ding Fenghua , Zhang Ruiyan
Published: October 2021

Vascular smooth muscle cell (VSMC) migration is an important step in the progression and development of vulnerable plaques. Thrombin is involved in both physiological and pathological processes of atherosclerosis. Therefore, the elucidation of the mechanisms underlying thrombin-induced VSMC migration is essential for devising effective treatments aimed at the prevention of plaque instability. In this study, we found that thrombin activated MAPK signaling pathways and increased the expression of galectin-3, which was also a well-known factor in atherosclerosis. Knockdown of galectin-3 by specific small interfering RNA (siRNA) blocked thrombin-induced activation of ERK1/2 and p38 MAPK, but not JNK MAPK. Src/FAK phosphorylation was also shown to be activated by thrombin. FAK autophosphorylation at Y397 was most significantly inhibited by galectin-3 siRNA. Galectin-3 siRNA or specific inhibitor (P38 MAPK inhibitor and ERK1/2 inhibitor) effectively prevented thrombin-induced VSMC migration via reducing paxillin expression. These findings demonstrate, for the first time, that thrombin stimulation of VSMC migration and paxillin expression are regulated by galectin-3, and ERK1/2, p38 MAPK, and Src/FAK signaling pathways are involved in this process. These results are beneficial to clarify the role of galectin-3 in thrombin-induced advanced lesions in atherosclerosis and shed new insights into the regulatory mechanism of VSMC migration in combating plaque rupture.
Case Report: Lithoplasty-Assisted Trans-Axillary Transcatheter Aortic Valve-in-Valve Implantation
Authors: Cerillo Alfredo Giuseppe , Pennesi Matteo , Iannone Luisa , Giustini Giorgia , de Cillis Paolo , Valenti Renato , Marchionni Niccolò , Stefano Pierluigi
Published: October 2021

We present the case of a severely symptomatic patient with a malfunctioning aortic bioprosthesis and severe multidistrict atherosclerosis that was addressed to our unit for transcatheter valve-in-valve implantation. The imaging and clinical assessment that led to the selection of the access route is discussed.
Quantitative Estimation on Contribution of Climate Changes and Watershed Characteristic Changes to Decreasing Streamflow in a Typical Basin of Yellow River
Authors: Lv Xizhi , Liu Shanshan , Li Shaopeng , Ni Yongxin , Qin Tianling , Zhang Qiufen
Published: October 2021

Climate changes and underlying surface of the watershed have affected the evolution of streamflow to a different degree. It is of great significance to quantitatively evaluate main drivers of streamflow change for development, utilization, and planning management of water resources. In this study, the Huangshui River basin, a typical basin of the Qinghai-Tibetan Plateau, China, was chosen as the research area. Huangshui is the largest first-class tributary in the upstream of the Yellow River. Based on the Budyko hypothesis, streamflow and meteorological datasets from 1958 to 2017 were used to quantitatively assess the relative contributions of changes in climate and watershed characteristics to streamflow change in research area. The results show that the streamflow of Huangshui River basin shows an insignificant decreasing trend; the sensitivity coefficients of streamflow to precipitation, potential evapotranspiration, and watershed characteristic parameter are 0.5502, −0.1055, and −183.2007, respectively. That is, 1 unit increase in precipitation would induce an increase of 0.5502 units in streamflow, and 1 unit increase in potential evapotranspiration would induce a decrease of 0.1055 units in streamflow, and an increase of 1 unit in the watershed characteristic coefficient would induce a decrease of 183.2007 units in streamflow. The streamflow decreased by 20.48 mm (13.59%) during the change period (1994–2017) compared with that during the reference period (1958–1993), which can be attributed to watershed characteristic changes (accounting for 73.64%) and climate change (accounting for 24.48%). Watershed characteristic changes exert a dominant influence upon the reduction of streamflow in the Huangshui River basin.
Readiness and Intention for Adapting New Normal COVID-19 Prevention Campaign for Sustainable Response Among Debre Berhan University Student’s During Campus Re-Entry: A Cross-Sectional Study
Authors: Taye Birhan Tsegaw , Mihret Muhabaw Shumye , Tiguh Agumas Eskezia , Dinberu Mesfin Tadese , Kitaw Tebabere Moltot , Tessema Saba Desta , Zerihun Mulualem Silesh , Haile Asalif Beyene , Worku Solomon Adanew , Amogne Fetene Kasahun , Amare Nakachew Sewnet , Demisse Tesfanesh Lemma , Ambaw Yeshinat Lakew , Dagnaw Abebe Mihretie , Ferede Addisu Andualem , Wondie Kindu Yinges , Kebede Azmeraw Ambachew
Published: October 2021

Background:The COVID-19 pandemic has had a profound effect on the general healthcare system and higher education worldwide. Adapting to the culture of “new normal,” an emerging response to COVID-19, is crucial for public health recovery and learning. This study investigated students' readiness and intention for adapting to the ‘‘new normal’’ COVID-19 prevention campaign during campus re-entry in Debre Berhan university in Ethiopia after the country eases lockdown restrictions.

Methods:A cross-sectional study was conducted from 20th to 30th January 2021, among graduate students in Debre Berhan university, Ethiopia. A simple random sampling technique was used to select 423 participants. A structured and pre-tested self-administered questionnaire was used to collect the data and bivariate and multivariable logistic regressions were fitted. Adjusted odds ratio (AOR) with a 95% confidence interval (CI) were used to interpret the strength of association and the statistical significance level was declared at a p-value of ≤0.05.

Result:In this study 423 participants were involved. The level of readiness and intention of adapting to the ‘‘new normal’’ prevention campaign were 49.4 and 54.8% respectively. Being a health science student (AOR = 1.82; 95% CI: 1.18, 2.81), being married (AOR = 2.10; 95% CI: 1.1, 4.05), having a smartphone (AOR = 1.84; 95% CI: 1.09, 3.12), and being knowledgeable towards COVID-19 (AOR = 1.56; 95% CI: 1.04, 2.34) were found to be significant factors associated with intention towards adapting to the ‘‘new normal’’ prevention practice. Also, the main reason why participants had no intention to carry out the ‘‘new normal’’ prevention campaign were a shortage of quality required preventive supplies (60%) and those who perceived themselves personally not at risk of COVID-19 (31.3%).

Conclusion:In this study, although information on the COVID-19 outbreak is continually evolving, readiness and intention for adapting to the ‘‘new normal’’ COVID-19 prevention campaign were insufficient. It is critical to improve readiness and intention through increasing knowledge and emphasizing the importance of new technologies and handy protective supplies that may encourage the sustainable practice of new norms post-pandemic.
Therapeutic Potential of Butyrate for Treatment of Type 2 Diabetes
Authors: Arora Tulika , Tremaroli Valentina
Published: October 2021

Metagenomics studies have shown that type 2 diabetes (T2D) is associated with an altered gut microbiota. Whereas different microbiota patterns have been observed in independent human cohorts, reduction of butyrate-producing bacteria has consistently been found in individuals with T2D, as well as in those with prediabetes. Butyrate is produced in the large intestine by microbial fermentations, particularly of dietary fiber, and serves as primary fuel for colonocytes. It also acts as histone deacetylase inhibitor and ligand to G-protein coupled receptors, affecting cellular signaling in target cells, such as enteroendocrine cells. Therefore, butyrate has become an attractive drug target for T2D, and treatment strategies have been devised to increase its intestinal levels, for example by supplementation of butyrate-producing bacteria and dietary fiber, or through fecal microbiota transplant (FMT). In this review, we provide an overview of current literature indicating that these strategies have yielded encouraging results and short-term benefits in humans, but long-term improvements of glycemic control have not been reported so far. Further studies are required to find effective approaches to restore butyrate-producing bacteria and butyrate levels in the human gut, and to investigate their impact on glucose regulation in T2D.
Wind Turbine Pitch System Fault Detection Using ssODM-DSTA
Authors: Tang Mingzhu , Hu Jiahao , Wu Huawei , Wang Zimin
Published: October 2021

A fault detection method of wind turbine pitch system using semi-supervised optimal margin distribution machine (ssODM) optimized by dynamic state transition algorithm (DSTA) [ssODM-DSTA] was proposed to solve the problem of obtaining the optimal hyperparameters of the fault detection model for the pitch system. This method was adopted to input the three hyperparameters of the ssODM into the dynamic state transition algorithm in the form of a three-dimensional vector to obtain the global optimal hyperparameters of the model, thus improving the performance of the fault detection model. Using a random forest to rank the priority of features of the pitch system fault data, the features with large weight proportions were retained. Then, the Pearson correlation method is used to analyze the degree of correlation among features, filter redundant features, and reduce the scale of features. The dataset was divided into a training dataset and a test dataset to train and test the proposed fault detection model, respectively. The real-time wind turbine pitch system fault data were collected from domestic wind farms to carry out fault detection experiments. The results have shown that the proposed method had a positive fault rate (FPR) and fault negative rate (FNR), compared with other optimization algorithms.
Carbon Neutrality Policies and Technologies: A Scientometric Analysis of Social Science Disciplines
Authors: Zhang Yuan , Pan Chung-Lien , Liao Han-Teng
Published: October 2021

Carbon neutrality, or “net zero”, has become the impact assessment project of human impact on Earth, increasingly structured to examine the implications, for the environment and people, of proposed actions and consequences of inaction. International and local collaboration efforts have been made with the aim of achieving carbon neutrality or “net-zero” emissions; thus, policies and technological innovations have been developed. Such impact-oriented risk assessment and control efforts amount to carbon-neutral pathways. Although such pathways may diverge in terms of energy, resources, and cost, it is critical to summarize essential and promising preparatory work on related policies and technologies to inform both policy-makers and social scientists to take actions. Through a scientometric analysis and systematic review of the latest social science literature, the study identified the size, scope and exemplar work for each social science discipline on carbon neutrality, based on 907 articles collected in early 2021 from the Web of Science database. This study reveals a set of disciplines focusing on certain common and distinct aspects of carbon neutrality. By outlining the possibilities and application areas for future research and policy development for socio-technical transition towards a net-zero or post-carbon future, this study has contributed to the understanding of the global efforts to achieve a clearer and viable carbon-neutral pathway. In conclusion, as many aspects of the planet and humans have become datafied, digitized, and networked, carbon neutrality, as the ecological indicator that guide human production and consumption patterns, must take on a central role in guiding our conscious green digital transformation of many political, economic, social and psychological aspects of our societies according to the existing and emerging social science knowledge.
Artificial Light at Night Impacts the Litter Layer Invertebrate Community With No Cascading Effects on Litter Breakdown
Authors: Hey Melissa H. , Epstein Howard E. , Haynes Kyle J.
Published: October 2021

Artificial light at night (ALAN) can impact the trophic structure of assemblages of ground-dwelling invertebrates, and changes in such assemblages can affect decomposition in terrestrial systems due to the various functional roles of these invertebrates, including microbial grazing, comminution of litter, and predation of other invertebrates, that can directly or indirectly affect plant-litter breakdown. Despite this, we are unaware of any studies that have evaluated the effects of ALAN on the breakdown of plant litter in a terrestrial ecosystem. We sought to answer whether ALAN affects litter breakdown via its effects on a community of ground-dwelling arthropods using two field experiments. In one experiment, we manipulated the presence of ALAN and the size classes of soil invertebrates that could enter mesh bags containing plant litter (litterbags). We found that the rate of plant-litter breakdown increased with the mesh size of litterbags but was unaffected by presence of ALAN. In a second field experiment carried out to examine the effects of ALAN on the trophic structure of litter-layer invertebrate communities, while controlling for potential effects of ALAN on vegetation, we again found that ALAN did not affect litter breakdown despite the fact that ALAN increased the abundances of secondary and tertiary consumers. Our finding that larger assemblages of ground-dwelling secondary and tertiary consumer invertebrates under ALAN did not slow litter breakdown through increased top-down control of detritivores suggests ALAN may disrupt predator-prey interactions in litter-layer communities.
Using Fay–Herriot Models and Variable Radius Plot Data to Develop a Stand-Level Inventory and Update a Prior Inventory in the Western Cascades, OR, United States
Authors: Temesgen Hailemariam , Mauro Francisco , Hudak Andrew T. , Frank Bryce , Monleon Vicente , Fekety Patrick , Palmer Marin , Bryant Timothy
Published: October 2021

Stands are the primary unit for tactical and operational forest planning. Forest managers can use remote-sensing-based forest inventories to precisely estimate attributes of interest at the stand scale. However, remote-sensing-based inventories typically rely on models relating remote-sensing information to forest attributes for fixed area plots with accurate coordinates. The collection of that kind of ground data is expensive and time-consuming. Furthermore, remote-sensing-based inventories provide precise descriptions of the forest when the remote-sensing data were collected, but they inevitably become outdated as the forest evolves. Fay–Herriot (FH), models can be used with ground information from variable radius plots even if the plot coordinates are unknown. Thus, they provide an efficient way to update old remote-sensing-based inventories or develop new ones when fixed radius plots are unavailable. In addition, FH models are well described in the small-area estimation literature and allow reporting estimation uncertainties, which is key to incorporating quality controls to remote-sensing inventories. We compared two scenarios developed in the Willamette National Forest, OR, United States, to produce stand-level estimates of above-ground biomass (AGB), and Volume (V) for natural and managed stands. The first, Case 1, was developed using auxiliary data from a recent lidar acquisition. The second, Case 2, was developed to update an old remote-sensing-based inventory. Results showed that FH models allowed for improvements in efficiency with respect to direct stand-level estimates obtained using only field data for both case scenarios and both typologies of stands. Average improvements in efficiency in natural stands were 37.36% for AGB and 33.10% for Volume for FH models from Case 1 and 20.19% for AGB and 19.25 for V for Case 2. For managed stands, average improvements for Case 1 were 2.29 and 19.92% for AGB and V, respectively, and for Case 2, improvements were 15.55% for AGB and 16.05% for V.
Autistic-Like Behavior and Impairment of Serotonin Transporter and AMPA Receptor Trafficking in N-Ethylmaleimide Sensitive Factor Gene-Deficient Mice
Authors: Xie Min-Jue , Iwata Keiko , Ishikawa Yasuyuki , Nomura Yuki , Tani Tomomi , Murata Koshi , Fukazawa Yugo , Matsuzaki Hideo
Published: October 2021

Autism spectrum disorder (ASD), characterized by profound impairment in social interactions and communication skills, is the most common neurodevelopmental disorder. Many studies on the mechanisms underlying the development of ASD have focused on the serotonergic system; however, these studies have failed to completely elucidate the mechanisms. We previously identified N-ethylmaleimide-sensitive factor (NSF) as a new serotonin transporter (SERT)-binding protein and described its importance in SERT membrane trafficking and uptake in vitro. In the present study, we generated Nsf+/- mice and investigated their behavioral, neurotransmitter, and neurophysiological phenotypes in vivo. Nsf+/- mice exhibited abnormalities in sociability, communication, repetitiveness, and anxiety. Additionally, Nsf loss led to a decrease in membrane SERT expression in the raphe and accumulation of glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors at the synaptic membrane surface in the hippocampal CA1 region. We found that postsynaptic density and long-term depression were impaired in the hippocampal CA1 region of Nsf+/- mice. Taken together, these findings demonstrate that NSF plays a role in synaptic plasticity and glutamatergic and serotonergic systems, suggesting a possible mechanism by which the gene is linked to the pathophysiology of autistic behaviors.
Applicability of Small-Molecule Inhibitors in the Study of Peptidyl Arginine Deiminase 2 (PAD2) and PAD4
Authors: Martín Monreal María Teresa , Rebak Alexandra Stripp , Massarenti Laura , Mondal Santanu , Šenolt Ladislav , Ødum Niels , Nielsen Michael L. , Thompson Paul R. , Nielsen Claus H. , Damgaard Dres
Published: October 2021

Citrullination, the conversion of peptidyl-arginine into peptidyl-citrulline, is involved in the breakage of self-tolerance in anti-CCP-positive rheumatoid arthritis. This reaction is catalyzed by peptidyl arginine deiminases (PADs), of which PAD2 and PAD4 are thought to play key pathogenic roles. Small-molecule PAD inhibitors such as the pan-PAD inhibitor BB-Cl-amidine, the PAD2-specific inhibitor AFM-30a, and the PAD4-specific inhibitor GSK199 hold therapeutic potential and are useful tools in studies of citrullination. Using an ELISA based on the citrullination of fibrinogen, we found that AFM-30a inhibited the catalytic activity of PADs derived from live PMNs or lysed PBMCs and PMNs and of PADs in cell-free synovial fluid samples from RA patients, while GSK199 had minor effects. In combination, AFM-30a and GSK199 inhibited total intracellular citrullination and citrullination of histone H3 in PBMCs, as determined by Western blotting. They were essentially nontoxic to CD4+ T cells, CD8+ T cells, B cells, NK cells, and monocytes at concentrations ranging from 1 to 20 μM, while BB-Cl-amidine was cytotoxic at concentrations above 1 μM, as assessed by flow cytometric viability staining and by measurement of lactate dehydrogenase released from dying cells. In conclusion, AFM-30a is an efficient inhibitor of PAD2 derived from PBMCs, PMNs, or synovial fluid. AFM-30a and GSK199 can be used in combination for inhibition of PAD activity associated with PBMCs but without the cytotoxic effect of BB-Cl-amidine. This suggests that AFM-30a and GSK199 may have fewer off-target effects than BB-Cl-amidine and therefore hold greater therapeutic potential.
Production of IL-6 and Phagocytosis Are the Most Resilient Immune Functions in Metabolically Compromised Human Monocytes
Authors: Krauss Pierre-Louis , Pfeiffenberger Moritz , Damerau Alexandra , Buttgereit Thomas , Chen Yuling , Gaber Timo , Buttgereit Frank
Published: October 2021

At sites of inflammation, monocytes carry out specific immune functions while facing challenging metabolic restrictions. Here, we investigated the potential of human monocytes to adapt to conditions of gradually inhibited oxidative phosphorylation (OXPHOS) under glucose free conditions. We used myxothiazol, an inhibitor of mitochondrial respiration, to adjust two different levels of decreased mitochondrial ATP production. At these levels, and compared to uninhibited OXPHOS, we assessed phagocytosis, production of reactive oxygen species (ROS) through NADPH oxidase (NOX), expression of surface activation markers CD16, CD80, CD11b, HLA-DR, and production of the inflammatory cytokines IL-1β, IL-6 and TNF-α in human monocytes. We found phagocytosis and the production of IL-6 to be least sensitive to metabolic restrictions while surface expression of CD11b, HLA-DR, production of TNF-α, IL-1β and production of ROS through NOX were most compromised by inhibition of OXPHOS in the absence of glucose. Our data demonstrate a short-term hierarchy of immune functions in human monocytes, which represents novel knowledge potentially leading to the development of new therapeutics in monocyte-mediated inflammatory diseases.
Transcriptomic Analysis Identifies A Tolerogenic Dendritic Cell Signature
Authors: Robertson Harry , Li Jennifer , Kim Hani Jieun , Rhodes Jake W. , Harman Andrew N. , Patrick Ellis , Rogers Natasha M.
Published: October 2021

Dendritic cells (DC) are central to regulating innate and adaptive immune responses. Strategies that modify DC function provide new therapeutic opportunities in autoimmune diseases and transplantation. Current pharmacological approaches can alter DC phenotype to induce tolerogenic DC (tolDC), a maturation-resistant DC subset capable of directing a regulatory immune response that are being explored in current clinical trials. The classical phenotypic characterization of tolDC is limited to cell-surface marker expression and anti-inflammatory cytokine production, although these are not specific. TolDC may be better defined using gene signatures, but there is no consensus definition regarding genotypic markers. We address this shortcoming by analyzing available transcriptomic data to yield an independent set of differentially expressed genes that characterize human tolDC. We validate this transcriptomic signature and also explore gene differences according to the method of tolDC generation. As well as establishing a novel characterization of tolDC, we interrogated its translational utility in vivo, demonstrating this geneset was enriched in the liver, a known tolerogenic organ. Our gene signature will potentially provide greater understanding regarding transcriptional regulators of tolerance and allow researchers to standardize identification of tolDC used for cellular therapy in clinical trials.
Easy or Not—The Advances of EZH2 in Regulating T Cell Development, Differentiation, and Activation in Antitumor Immunity
Authors: Huang Jiaqi , Zhang Jie , Guo Zhengyang , Li Chen , Tan Zhen , Wang Junjie , Yang Jianling , Xue Lixiang
Published: October 2021

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2), which regulates downstream gene expression by trimethylation of lysine 27 in histone H3 (H3K27me3). EZH2 mutations or overexpressions are associated with many types of cancer. As inhibition of EZH2 activity could upregulate the expression of tumor suppressor genes, EZH2 has recently become an interesting therapeutic target for cancer therapy. Moreover, accumulating evidence has shown that EZH2 may contribute to the regulation of immune cells, especially T cells. EZH2 regulates T cell development, differentiation, and function, suggesting that EZH2 also regulates immune homeostasis in addition to tumor suppressor genes. Moreover, EZH2 can regulate T cell fate by targeting non-T cell factors such as metabolism, cytokines, and myeloid-derived suppressor cells. The role of EZH2 in this process has not been fully addressed. This review discusses up-to-date research on EZH2-mediated regulation of immunological function and the progress of immunological therapeutic strategies based on this regulation.
Patient-Derived Bone Marrow Spheroids Reveal Leukemia-Initiating Cells Supported by Mesenchymal Hypoxic Niches in Pediatric B-ALL
Authors: Balandrán Juan Carlos , Dávila-Velderrain José , Sandoval-Cabrera Antonio , Zamora-Herrera Gabriela , Terán-Cerqueda Vanessa , García-Stivalet Lilia Adela , Limón-Flores José Alejandro , Armenta-Castro Erick , Rodríguez-Martínez Aurora , Leon-Chavez Bertha Alicia , Vallejo-Ruiz Verónica , Hassane Duane C. , Pérez-Tapia Sonia Mayra , Ortiz-Navarrete Vianney , Guzman Monica L. , Pelayo Rosana
Published: October 2021

B-cell acute lymphoblastic leukemia (B-ALL) results from the expansion of malignant lymphoid precursors within the bone marrow (BM), where hematopoietic niches and microenvironmental signals provide leukemia-initiating cells (LICs) the conditions to survive, proliferate, initiate disease, and relapse. Normal and malignant lymphopoiesis are highly dependent on the BM microenvironment, particularly on CXCL12-abundant Reticular (CAR) cells, which provide a niche for maintenance of primitive cells. During B-ALL, leukemic cells hijack BM niches, creating a proinflammatory milieu incompetent to support normal hematopoiesis but favoring leukemic proliferation. Although the lack of a phenotypic stem cell hierarchy is apparent in B-ALL, LICs are a rare and quiescent population potentially responsible for chemoresistance and relapse. Here, we developed novel patient-derived leukemia spheroids (PDLS), an ex vivo avatar model, from mesenchymal stromal cells (MSCs) and primary B-ALL cells, to mimic specialized niche structures and cell-to-cell intercommunication promoting normal and malignant hematopoiesis in pediatric B-ALL. 3D MSC spheroids can recapitulate CAR niche-like hypoxic structures that produce high levels of CXCL10 and CXCL11. We found that PDLS were preferentially enriched with leukemia cells displaying functional properties of LICs, such as quiescence, low reactive oxygen species, drug resistance, high engraftment in immunodeficient mice, and long-term leukemogenesis. Moreover, the combination of PDLS and patient-derived xenografts confirmed a microenvironment-driven hierarchy in their leukemic potential. Importantly, transcriptional profiles of MSC derived from primary patient samples revealed two unique signatures (1), a CXCL12low inflammatory and leukemia expansion (ILE)-like niche, that likely supports leukemic burden, and (2) a CXCL11hi immune-suppressive and leukemia-initiating cell (SLIC)-like niche, where LICs are likely sustained. Interestingly, the CXCL11+ hypoxic zones were recapitulated within the PDLS that are capable of supporting LIC functions. Taken together, we have implemented a novel PDLS system that enriches and supports leukemia cells with stem cell features driven by CXCL11+ MSCs within hypoxic microenvironments capable of recapitulating key features, such as tumor reemergence after exposure to chemotherapy and tumor initiation. This system represents a unique opportunity for designing ex vivo personalized avatars for B-ALL patients to evaluate their own LIC pathobiology and drug sensitivity in the context of the tumor microenvironment.
The Role of Plasmacytoid Dendritic Cells in Cancers
Authors: Zhou Binhui , Lawrence Toby , Liang Yinming
Published: October 2021

Plasmacytoid dendritic cells (pDCs) are a special subtype of dendritic cells with the morphology of plasma cells. pDCs produce massive amounts of type I interferon (IFN-I), which was originally found to play an extremely pivotal role in antiviral immunity. Interestingly, accumulated evidence indicates that pDCs can also play an important role in tumorigenesis. In the human body, most of the IFN-α is secreted by activated pDCs mediated by toll-like receptor (TLR) stimulation. In many types of cancer, tumors are infiltrated by a large number of pDCs, however, these pDCs exhibit no response to TLR stimulation, and reduced or absent IFN-α production. In addition, tumor-infiltrating pDCs promote recruitment of regulatory T cells (Tregs) into the tumor microenvironment, leading to immunosuppression and promoting tumor growth. In this review, we discuss recent insights into the development of pDCs and their roles in a variety of malignancies, with special emphasis on the basic mechanisms.
Dynamics of Vascular Protective and Immune Supportive Sphingosine-1-Phosphate During Cardiac Surgery
Authors: Greiwe Gillis , Moritz Eileen , Amschler Katharina , Poppe Annika , Sarwari Harun , Nierhaus Axel , Kluge Stefan , Reichenspurner Hermann , Zoellner Christian , Schwedhelm Edzard , Daum Günter , Tampe Björn , Winkler Martin Sebastian
Published: October 2021

Introduction

Sphingosine-1-phosphate (S1P) is a signaling lipid and crucial in vascular protection and immune response. S1P mediated processes involve regulation of the endothelial barrier, blood pressure and S1P is the only known inducer of lymphocyte migration. Low levels of circulatory S1P correlate with severe systemic inflammatory syndromes such as sepsis and shock states, which are associated with endothelial barrier breakdown and immunosuppression. We investigated whether S1P levels are affected by sterile inflammation induced by cardiac surgery.

Materials and Methods

In this prospective observational study we included 46 cardiac surgery patients, with cardiopulmonary bypass (CPB, n=31) and without CPB (off-pump, n=15). Serum-S1P, S1P-sources and carriers, von-Willebrand factor (vWF), C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) were measured at baseline, post-surgery and at day 1 (POD 1) and day 4 (POD 4) after surgical stimulus.

Results

Median S1P levels at baseline were 0.77 nmol/mL (IQR 0.61-0.99) and dropped significantly post-surgery. S1P was lowest post-surgery with median levels of 0.37 nmol/mL (IQR 0.31-0.47) after CPB and 0.46 nmol/mL (IQR 0.36-0.51) after off-pump procedures (P<0.001). The decrease of S1P was independent of surgical technique and observed in all individuals. In patients, in which S1P levels did not recover to preoperative baseline ICU stay was longer and postoperative inflammation was more severe. S1P levels are associated with its sources and carriers and vWF, as a more specific endothelial injury marker, in different phases of the postoperative course. Determination of S1P levels during surgery suggested that also the anticoagulative effect of heparin might influence systemic S1P.

Discussion

In summary, serum-S1P levels are disrupted by major cardiac surgery. Low S1P levels post-surgery may play a role as a new marker for severity of cardiac surgery induced inflammation. Due to well-known protective effects of S1P, low S1P levels may further contribute to the observed prolonged ICU stay and worse clinical status. Moreover, we cannot exclude a potential inhibitory effect on circulating S1P levels by heparin anticoagulation during surgery, which would be a new pro-inflammatory pleiotropic effect of high dose heparin in patients undergoing cardiac surgery.
Estimating Cetacean Bycatch From Non-representative Samples (I): A Simulation Study With Regularized Multilevel Regression and Post-stratification
Authors: Authier Matthieu , Rouby Etienne , Macleod Kelly
Published: October 2021

Bycatch, the non-intentional capture or killing of non-target species in commercial or recreational fisheries, is a world wide threat to protected, endangered or threatened species (PETS) of marine megafauna. Obtaining accurate bycatch estimates of PETS is challenging: the only data available may come from non-dedicated schemes, and may not be representative of the whole fisheries effort. We investigated, with simulated data, a model-based approach for estimating PETS bycatch from non-representative samples. We leveraged recent development in the statistical analysis of surveys, namely regularized multilevel regression with post-stratification, to infer total bycatch under realistic scenarios of data sampling such as under-sampling or over-sampling when PETS bycatch risk is high. Post-stratification is a survey technique to re-align the sample with the population and addresses the problem of non-representative samples. Post-stratification requires to sub-divide a population of interest into potentially hundreds of cells corresponding to the cross-classification of important attributes. Multilevel regression accommodate this data structure, and the statistical technique of regularization can be used to predict for each of these hundreds of cells. We illustrated these statistical ideas by modeling bycatch risk for each week within a year with as few as a handful of observed PETS bycatch events. The model-based approach led to improvements, under mild assumptions, both in terms of accuracy and precision of estimates and was more robust to non-representative samples compared to more design-based methods currently in use. In our simulations, there was no detrimental effects of using the model-based even when sampling was representative. Estimating PETS bycatch ideally requires dedicated observer schemes and adequate coverage of fisheries effort. We showed how a model-based approach combining sparse data typical of PETS bycatch and recent methodological developments can help when both dedicated observer schemes and adequate coverage are challenging to implement.
Simultaneous Occurrence of Tropical Cyclones in the Northern Indian Ocean: Differential Response and Triggering Mechanisms
Authors: Roy Chowdhury Riyanka , Prasanna Kumar S. , Chakraborty Arun
Published: October 2021

The northern Indian Ocean, comprising of two marginal seas, the Arabian Sea (AS) and the Bay of Bengal (BoB), is known for the occurrence of tropical cyclones. The simultaneous occurrence of the cyclones Luban in the AS and Titli in the BoB is a rare phenomenon, and, in the present study, we examined their contrasting upper ocean responses and what led to their formation in October 2018. Being a category-2 cyclone, the maximum cooling of sea surface temperature associated with Titli was 1°C higher than that of Luban, a category-1 cyclone. The higher tropical cyclone heat potential in the BoB compared with the AS was one of the reasons why Titli was more intense than Luban. The enhancement of chlorophylla(Chl-a) and net primary productivity (NPP) by Luban was 2- and 3.7-fold, respectively, while that by Titli was 3- and 5-fold, respectively. Despite this, the magnitudes of both Chl-aand NPP were higher in the AS compared with the BoB. Consistent with physical and biological responses, the CO2outgassing flux associated with Titli was 12-fold higher in comparison to the pre-cyclone value, while that associated with Luban was 10-fold higher. Unlike the Chl-aand NPP, the magnitude of CO2flux in the BoB was higher than that in the AS. Although the cyclones Luban and Titli originated simultaneously, their generating mechanisms were quite different. What was common for the genesis of both cyclones was the pre-conditioning of the upper ocean in 2018 by the co-occurrence of El Niño and the positive phase of Indian Ocean dipole along with the cold phase of the Pacific decadal oscillation, all of which worked in tandem and warmed the AS and parts of the BoB. What triggered the genesis of Luban in the AS was the arrival of the Madden–Julian oscillation (MJO) and the mixed Rossby-gravity wave during the first week of October. The genesis of Titli in the BoB was triggered by the eastward propagation of the MJO and the associated enhanced convection from the AS into the region of origin of Titli along with the arrival of the downwelling oceanic Rossby wave.
Multi-Species Feeding Association Dynamics Driven by a Large Generalist Predator
Authors: Gostischa Julia , Massolo Alessandro , Constantine Rochelle
Published: October 2021

Multi-species feeding associations (MSFAs) are temporary communities of animals exploiting the same or co-occurrent resources. Their dynamics are species dependent, often creating competitive interactions, but they can also increase foraging efficiency and ultimately individual fitness. The foraging behaviors of some species can enhance prey capture by others, with different roles depending on the species present. Here, we use the Hauraki Gulf, New Zealand, as a model system to quantitatively characterize the principal types of MSFAs between 2011 and 2020. We determine the foraging associations of a large generalist predator, the Bryde’s whale, and how shifts in its prey preference change the dynamics between seabird competitors. Hierarchical clustering from influential predator groups identified three types of MSFAs. Two of mainly fish-feeding predators, one including and one lacking Bryde’s whales, and one involving (although not limited to) plankton-feeders associated with Bryde’s whales. Cluster frequencies featured significant temporal trends, whereas MSFA diversity and whale association rate showed no significant changes. Bryde’s whales’ increasing reliance on zooplankton highlights their foraging plasticity, with changes in cluster frequencies and resource competition related to this shift from fish to zooplankton. The role of Bryde’s whales varies from joiners and terminators in fish-feeding aggregations to initiators with plankton-feeding seabird associations, thereby changing the MSFA dynamics. MSFAs tend toward a diversity equilibrium, i.e., a maximum number of species involved before competitive effects exceed the benefits of interaction. Functional MSFAs where heterospecific interactions are important to foraging success can be affected by changing composition. Future work should focus on the behavioral interactions between key predators, prey availability and their effect on MSFAs.
A Review of the Opportunities and Challenges for Using Remote Sensing for Management of Surface-Canopy Forming Kelps
Authors: Cavanaugh Kyle C. , Bell Tom , Costa Maycira , Eddy Norah E. , Gendall Lianna , Gleason Mary G. , Hessing-Lewis Margot , Martone Rebecca , McPherson Meredith , Pontier Ondine , Reshitnyk Luba , Beas-Luna Rodrigo , Carr Mark , Caselle Jennifer E. , Cavanaugh Katherine C. , Flores Miller Rebecca , Hamilton Sara , Heady Walter N. , Hirsh Heidi K. , Hohman Rietta , Lee Lynn Chi , Lorda Julio , Ray James , Reed Daniel C. , Saccomanno Vienna R. , Schroeder Sarah B.
Published: October 2021

Surface-canopy forming kelps provide the foundation for ecosystems that are ecologically, culturally, and economically important. However, these kelp forests are naturally dynamic systems that are also threatened by a range of global and local pressures. As a result, there is a need for tools that enable managers to reliably track changes in their distribution, abundance, and health in a timely manner. Remote sensing data availability has increased dramatically in recent years and this data represents a valuable tool for monitoring surface-canopy forming kelps. However, the choice of remote sensing data and analytic approach must be properly matched to management objectives and tailored to the physical and biological characteristics of the region of interest. This review identifies remote sensing datasets and analyses best suited to address different management needs and environmental settings using case studies from the west coast of North America. We highlight the importance of integrating different datasets and approaches to facilitate comparisons across regions and promote coordination of management strategies.
Prediction of Inclusion Types From BSE Images: RF vs. CNN
Authors: Abdulsalam Mohammad , Gao Nan , Webler Bryan A. , Holm Elizabeth A.
Published: October 2021

The analysis of non-metallic inclusions is crucial for the assessment of steel properties. Scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS) is one of the most prominent methods for inclusion analysis. This study utilizes the output generated from SEM/EDS analysis to predict inclusion types from BSE images. Prediction models were generated using two different algorithms, Random Forest (RF) and convolutional neural networks (CNN), for comparison. For each method, three separate models were developed. Starting with a simple binary model to differentiate between inclusions and non-inclusions, then developing to more complex four and five class models. For the 4-class model, inclusions were split into oxides, sulfides, and oxy-sulfides, in addition to the non-inclusion class. The 5-class model included specific types of inclusions only, namely alumina, calcium aluminates, calcium sulfides, complex calcium-manganese sulfides, and oxy-sulfide inclusions. CNN achieved better accuracy for the binary (92%) and 4-class (78%) models, compared to RF (binary 87%, 4-class 75%). For the 5-class model, the results were similar, 60% accuracy for RF and 59% for CNN.
Lung Tissue Microbiome Is Associated With Clinical Outcomes of Idiopathic Pulmonary Fibrosis
Authors: Yoon Hee-Young , Moon Su-Jin , Song Jin Woo
Published: October 2021

Background: Several studies using bronchoalveolar lavage fluid (BALF) reported that lung microbial communities were associated with the development and clinical outcome of idiopathic pulmonary fibrosis (IPF). However, the microbial communities in IPF lung tissues are not well known. This study is aimed to investigate bacterial microbial communities in lung tissues and determine their impact on the clinical outcomes of patients with IPF.

Methods: Genomic DNA extracted from lung tissues of patients with IPF (n = 20; 10 non-survivors) and age- and sex-matched controls (n = 20) was amplified using fusion primers targeting the V3 and V4 regions of the 16S RNA genes with indexing barcodes.

Results: Mean age of IPF subjects was 63.3 yr, and 65% were male. Alpha diversity indices did not significantly differ between IPF patients and controls, or between IPF non-survivors and survivors. The relative abundance of Lactobacillus, Paracoccus, and Akkermansia was increased, whereas that of Caulobacter, Azonexus, and Undibacterium decreased in patients with IPF compared with that in the controls. A decreased relative abundance of Pelomonas (odds ratio [OR], 0.352, p = 0.027) and Azonexus (OR, 0.013, p = 0.046) was associated with a diagnosis of IPF in the multivariable logistic analysis adjusted by age and gender. Multivariable Cox analysis adjusted for age and forced vital capacity (FVC) revealed that higher relative abundance of Streptococcus (hazard ratio [HR], 1.993, p = 0.044), Sphingomonas (HR, 57.590, p = 0.024), and Clostridium (HR, 37.189, p = 0.038) was independently associated with IPF mortality. The relative abundance of Curvibacter (r = 0.590) and Thioprofundum (r = 0.373) was correlated positively, whereas that of Anoxybacillus (r = −0.509) and Enterococcus (r = −0.593) was correlated inversely with FVC. In addition, the relative abundance of the Aquabacterium (r = 0.616) and Peptoniphilus (r = 0.606) genera was positively correlated, whereas that of the Fusobacterium (r = −0.464) and Phycicoccus (r = −0.495) genera was inversely correlated with distance during the 6-min walking test.

Conclusions: The composition of the microbiome in lung tissues differed between patients with IPF and controls and was associated with the diagnosis, mortality, and disease severity of IPF.