bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate and Health in Buenos Aires: A Review on Climate Impact on Human Health Studies Between 1995 and 2015
Authors: Fontan Silvia , Rusticucci Matilde
Published: February 2021

In this review, seven pieces of research on climate variability and its impact on human health in Buenos Aires City between 1995 and 2015 were evaluated. The review highlighted continuities and ruptures in the methodology, variables, and statistics data of the research, considering their similarities and differences in the period of study and the methodology applied. Contributions, pending issues, and public policies on climate change challenges in the city aimed at improving living conditions were considered. Six studies contributed evidence on the relationship between climate and health and its impacts on the population; two studies suggested the development of early warning systems and one study is a preliminary approach.
Drought and Water Scarcity Management Policy in England and Wales—Current Failings and the Potential of Civic Innovation
Authors: Grecksch Kevin , Landström Catharina
Published: February 2021

Drought management in England and Wales takes place in a narrow, confined governance space. Assessed against current literature on drought management, England and Wales show little innovativeness and little actual willingness to change. We ask how drought and water scarcity management is currently done, who is involved (or not) and, foremost, what are the current problems and deficiencies with current English and Welsh drought and water scarcity management that require attention. We are also interested in the question of what can be done to improve drought and water scarcity management in England and Wales. This research therefore explores how we can create a continuous relationship between the different actors contributing different levels of knowledge and we plead to widen the drought governance space in order to face the current and future water governance challenges. First, we present an empirically based critique of current drought and water scarcity management in England and Wales, highlighting the contrast between available drought and water scarcity management options and what is currently applied in England and Wales. Second, we present and introduce Environmental Competency Groups, a methodology aiming to bring local residents’ experience-based knowledge of water management in relation to particular catchments to bear on the generation of scientific knowledge. It has been successfully trialed in relation to both droughts and flooding in England and Wales. We argue that this is a successful way to bring together people with different perspectives and knowledge in order to overcome the deficiencies of current drought and water scarcity management in England and Wales.
Screening for High-Risk Marine Invaders in the Hudson Bay Region, Canadian Arctic
Authors: Goldsmit Jesica , McKindsey Christopher W. , Stewart D. Bruce , Howland Kimberly L.
Published: February 2021

The Canadian Arctic is receiving increased ship traffic, largely related to non-renewable resource exploitation and facilitated by climate change. This traffic, much of which arrives in ballast, increases opportunities for the spread of aquatic invasive species (AIS). One of the regions at greatest risk is the Hudson Bay Complex. A horizon scanning exercise was conducted using the semi-quantitative Canadian Marine Invasive Screening Tool (CMIST) to identify AIS of potential concern to the region. This screening-level risk assessment tool, uses documented information to answer questions related to the likelihood and impact of invasion. Species were analyzed by ecological categories (zoobenthos, zooplankton, phytobenthos) and taxonomic groups, with 14 species (out of 31) identified as being of highest relative risk. Crabs, mollusks, macrozooplankton and macroalgae were the taxonomic groups with the highest overall risk scores, through a combination of higher likelihood of invasion and impact scores relative to other taxa. Species that may pose the highest AIS risk are currently mainly distributed on the east and west coasts of the North Atlantic Ocean. Their distributions coincide with source ports and shipping pathways that are well connected to the Hudson Bay Complex. This first horizon scan to identify potential high-risk AIS for the Canadian Arctic incorporated two novel approaches into the CMIST analysis: i) use of the tool to assess two new ecological categories (phytobenthos and zooplankton), and ii) use of averaged CMIST results to interpret general risk patterns of ecological categories. This study is also the first to use CMIST scores to highlight common source regions and connected ports for the highest risk species. In a scenario of climate change and increasing ship traffic, this information can be used to support management actions such as the creation of watch lists to inform adaptive management for preventing AIS establishment, and mitigating associated environmental and economic impacts.
Extramatrical Mycelium and Ectomycorrhizal Community Composition of Quercus pubescens in a Sub-Mediterranean Stress-Prone Environment
Authors: Mrak Tanja , Šibanc Nataša , Brailey-Jones Philip , Štraus Ines , Gričar Jožica , Kraigher Hojka
Published: February 2021

Temporal studies that would offer insight into resilience of ectomycorrhizal (ECM) communities in stress prone climates are scarce despite their role in tree nutrition and water supply. Our study characterized the vitality, community composition, diversity, and function ofQuercus pubescensWilld. ECM fungi in the Sub-Mediterranean stress-prone environment for 2 consecutive years (June 2016–May 2018) and related the investigated measures to environmental parameters. ECM community was assessed for species actively associating with root tips and exploring the soil volume through the assessment of mycelial ingrowth into sand-filled mesh bags. The investigated period was characterized by a drier than average summer combined with wildfire in 2016 followed by another dry summer in 2017. The vital to non-vital ECM root tip ratio decreased below one in August 2016 and remained low until January 2018. This was ascribed to a series of stress events that occurred at the site including sequential droughts and wildfire. The most abundant ECM lineages on root tips wereTomentellaand other Thelephoraceae,Sebacina, andCenococcumwhile in mesh bags the most abundant wereTomentella, Sebacina, Pseudotomentella, Pyronemataceae,Inocybe, Cortinarius, Agaricales, and Boletales lineages. High intra-site variability was observed, with ECM communities directly associated with root tips and exploring the soil volume varying significantly among the plots. Community composition was stable over time, while species richness varied with mean air and soil temperature, relative air humidity, and solar radiation. The most abundant exploration type observed at this site was short distance, which was associated with precipitation along with long distance exploration type. The medium distance exploration type was temporally variable and responded to soil temperature and relative air humidity reflecting seasonality at the site. The presented results indicate complex relationships between environmental parameters, abiotic stress, and ECM fungi.
Amazonia Seasons Have an Influence in the Composition of Bacterial Gut Microbiota of Mangrove Oysters (Crassostrea gasar)
Authors: Conceição Marcos Vinícius Reis , Costa Sávio Souza , Schaan Ana Paula , Ribeiro-dos-Santos Ândrea Kely Campos , Silva Artur , das Graças Diego Assis , Schneider Maria Paula Cruz , Baraúna Rafael Azevedo
Published: February 2021

The mangrove oysters (Crassostrea gasar) are molluscs native to the Amazonia region and their exploration and farming has increased considerably in recent years. These animals are farmed on beds built in the rivers of the Amazonia estuaries and, therefore, the composition of their microbiome should be directly influenced by environmental conditions. Our work aimed to evaluate the changes in bacterial composition of oyster's microbiota at two different seasons (rainy and dry). For this purpose, we amplified and sequenced the V3-V4 regions of the 16S rRNA gene. Sequencing was performed on the Illumina MiSeq platform. According to the rarefaction curve, the sampling effort was sufficient to describe the bacterial diversity in the samples. Alpha-diversity indexes showed that the bacterial microbiota of oysters is richer during the rainy season. This richness is possibly associated with the diversity at lower taxonomic levels, since the relative abundance of bacterial phyla in the two seasons remained relatively constant. The main phyla found include Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Similar results were found for the species Crassostrea gigas, Crassostrea sikamea, and Crassostrea corteziensis. Beta-diversity analysis showed that the bacterial composition of oyster's gut microbiota was quite different in the two seasons. Our data demonstrate the close relationship between the environment and the microbiome of these molluscs, reinforcing the need for conservation and sustainable management of estuaries in the Amazonia.
Human Mesenchymal Stem Cell-Derived Exosomal microRNA-143 Promotes Apoptosis and Suppresses Cell Growth in Pancreatic Cancer via Target Gene Regulation
Authors: Wang Bingyi , Xu Yan , Wei Yuhua , Lv Lixin , Liu Nanbin , Lin Rui , Wang Xiuyan , Shi Baomin
Published: February 2021

Background

This study aimed to explore the regulatory mechanism of hsa-miR-143-3p and lncRNA RP11-363N22.3–functioning upstream ofKRAS–in exosomes derived from human mesenchymal stem cells (hMSCs) in pancreatic cancer.

Methods

Western blotting and quantitative PCR were used to determine gene expression.In vitro, cell proliferation, apoptosis, and cell cycle and invasion were evaluated using CCK-8 assay, flow cytometry, and transwell assays, respectively.In vivo, the effect of hsa-miR143-3p was investigated using a tumorigenesis test in nude mice. The association between hsa-miR-143-3p and lncRNA RP11-363N22.3 was investigated using the dual-luciferase assay.

Results

hsa-miR-143-3p expression significantly increased in hMSC exosomes than in those in human pancreatic cancer cell line (CFPAC-1) exosomes.In vitro, compared to the MOCK (CFPAC-1 only) group, cell proliferation and invasion were inhibited and apoptosis was induced in the inhibitor NC (CFPAC-1 + MSC-hsa-miR-3p inhibitor NC) group, while these changes were reversed in the inhibitor (CFPAC-1 + MSC-hsa-miR-3p inhibitor) group. The expression of lncRNA RP11-363N22.3 and genes related to miR-143 significantly decreased in the inhibitor NC group compared to the MOCK group, and increased in the inhibitor group compared to inhibitor NC group. A targeted combinatorial effect was observed between lncRNA RP11-363N22.3 and hsa-miR-143-3p.In vivo, the tumor volume of the mimics (CFPAC-1 + MSC-hsa-miR-143-3p mimics) group was smaller than that of the mimics NC (CFPAC-1 + MSC-hsa-miR-143-3p mimics NC) and MOCK groups. H&E staining showed that there were no obvious pathological changes in MOCK and mimic NC groups, while cell necrosis was seen in some regions in mimic groups.

Conclusion

hsa-miR-143-3p may promote apoptosis and suppress cell growth and invasion in pancreatic cancer.
Combined Low-/High-Density Modern and Ancient Genome-Wide Data Document Genomic Admixture History of High-Altitude East Asians
Authors: Liu Yan , Wang Mengge , Chen Pengyu , Wang Zheng , Liu Jing , Yao Lilan , Wang Fei , Tang Renkuan , Zou Xing , He Guanglin
Published: February 2021

The Tibetan Plateau (TP) is considered to be one of the last terrestrial environments conquered by the anatomically modern human. Understanding of the genetic background of highland Tibetans plays a pivotal role in archeology, anthropology, genetics, and forensic investigations. Here, we genotyped 22 forensic genetic markers in 1,089 Tibetans residing in Nagqu Prefecture and collected 1,233,013 single nucleotide polymorphisms (SNPs) in the highland East Asians (Sherpa and Tibetan) from the Simons Genome Diversity Project and ancient Tibetans from Nepal and Neolithic farmers from northeastern Qinghai-Tibetan Plateau from public databases. We subsequently merged our two datasets with other worldwide reference populations or eastern ancient Eurasians to gain new insights into the genetic diversity, population movements, and admixtures of high-altitude East Asians via comprehensive population genetic statistical tools [principal component analysis (PCA), multidimensional scaling plot (MDS), STRUCTURE/ADMIXTURE, f3, f4, qpWave/qpAdm, and qpGraph]. Besides, we also explored their forensic characteristics and extended the Chinese National Database based on STR data. We identified 231 alleles with the corresponding allele frequencies spanning from 0.0005 to 0.5624 in the forensic low-density dataset, in which the combined powers of discrimination and the probability of exclusion were 1–1.22E-24 and 0.999999998, respectively. Additionally, comprehensive population comparisons in our low-density data among 57 worldwide populations via the Nei’s genetic distance, PCA, MDS, NJ tree, and STRUCTURE analysis indicated that the highland Tibeto-Burman speakers kept the close genetic relationship with ethnically close populations. Findings from the 1240K high-density dataset not only confirmed the close genetic connection between modern Highlanders, Nepal ancients (Samdzong, Mebrak, and Chokhopani), and the upper Yellow River Qijia people, suggesting the northeastern edge of the TP served as a geographical corridor for ancient population migrations and interactions between highland and lowland regions, but also evidenced that late Neolithic farmers permanently colonized into the TP by adopting cold-tolerant barley agriculture that was mediated via the acculturation of idea via the millet farmer and not via the movement of barley agriculturalist as no obvious western Eurasian admixture signals were identified in our analyzed modern and ancient populations. Besides, results from the qpAdm-based admixture proportion estimation and qpGraph-based phylogenetic relationship reconstruction consistently demonstrated that all ancient and modern highland East Asians harbored and shared the deeply diverged Onge/Hoabinhian-related eastern Eurasian lineage, suggesting a common Paleolithic genetic legacy existed in high-altitude East Asians as the first layer of their gene pool.
Analysis of MicroRNAs Associated With Carotid Atherosclerotic Plaque Rupture With Thrombosis
Authors: Nie Peng , Yang Fan , Wan Fang , Jin Shuxuan , Pu Jun
Published: February 2021

Atherosclerosis is a progressive vascular wall inflammatory disease, and the rupture of atherosclerotic vulnerable plaques is the leading cause of morbidity and mortality worldwide. This study intended to explore the potential mechanisms behind plaque rupture and thrombosis in ApoE knockout mice. The spontaneous plaque rupture models were established, and left carotid artery tissues at different time points (1-, 2-, 4-, 6-, 8-, 12-, and 16-week post-surgery) were collected. By the extent of plaque rupture, plaque was defined as (1) control groups, (2) atherosclerotic plaque group, and (3) plaque rupture group. Macrophage (CD68), MMP-8, and MMP-13 activities were measured by immunofluorescence. Cytokines and inflammatory markers were measured by ELISA. The left carotid artery sample tissue was collected to evaluate the miRNAs expression level by miRNA-microarray. Bioinformatic analyses were conducted at three levels: (2) vs. (1), (3) vs. (2), and again in seven time series analysis. The plaque rupture with thrombus and intraplaque hemorrhage results peaked at 8 weeks and decreased thereafter. Similar trends were seen in the number of plaque macrophages and lipids, the expression of matrix metalloproteinase, and the atherosclerotic and plasma cytokine levels. MiRNA-microarray showed that miR-322-5p and miR-206-3p were specifically upregulated in the atherosclerotic plaque group compared with those in the control group. Meanwhile, miR-466h-5p was specifically upregulated in the plaque rupture group compared with the atherosclerotic plaque group. The highest incidence of plaque rupture and thrombosis occurred at 8 weeks post-surgery. miR-322-5p and miR-206-3p may be associated with the formation of atherosclerotic plaques. miR-466h-5p may promote atherosclerotic plaque rupture via apoptosis-related pathways.
Mutational Spectrum of LDLR and PCSK9 Genes Identified in Iranian Patients With Premature Coronary Artery Disease and Familial Hypercholesterolemia
Authors: Moradi Arman , Maleki Majid , Ghaemmaghami Zahra , Khajali Zahra , Noohi Feridoun , Moghadam Maryam Hosseini , Kalyinia Samira , Mowla Seyed Javad , Seidah Nabil G. , Malakootian Mahshid
Published: February 2021

Familial hypercholesterolemia (FH) is a common, yet underdiagnosed, genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol levels, which can increase the risk of early-onset coronary artery disease (CAD). In the present study, we screened the nucleotide variations of the LDLR and PCSK9 genes, as well as a part of the APOB gene, in Iranian patients with FH and premature CAD to find the genetic cause of the disorder. Fifteen unrelated individuals with a clinical diagnosis of FH and premature CAD were recruited. Direct DNA sequencing was applied to screen the whole coding exons and exon–intron boundaries of the LDLR and PCSK9 genes and the main parts of their introns, together with exon 26 of the APOB gene. The pathogenicity of the identified mutations was investigated via either segregation analyses in the family or in silico predictive software. Six different point mutations (p.Cys148Tyr, p.Cys216Tyr, p.Cys302Trp, p.Cys338Trp, p.Leu479Gln, and p.G593Afs∗72) in LDLR and a double mutation (p.Asp172His and p.Ala53Val) in both LDLR and PCSK9 genes were identified in seven families with clinically diagnosed FH (43%), whereas no pathogenic mutations were found in eight families with clinically diagnosed FH. This study is the first to identify 1 pathogenic mutation in the LDLR gene (c.1014C > G [p.Cys338Trp]) and to cosegregate it from the affected individual in the family. No mutations were found in the APOB gene, whereas several silent mutations/polymorphisms were identified in the LDLR and PCSK9 genes. Genetic testing and reports on nucleotide alterations in the Iranian population are still limited. Our findings not only further confirm the significant role of FH in the incidence of premature CAD but also enlarge the spectrum of LDLR and PCSK9 variations and exhibit the heterogeneity of FH in Iranians. In patients with no mutation in the examined genes, the disease could be begotten either by a polygenic cause or by gene defects occurring in other related genes and regions not targeted in this study.
Integrated Analysis of the Prognosis-Associated RNA-Binding Protein Genes and Candidate Drugs in Renal Papillary Cell Carcinoma
Authors: Jiang Silin , Ren Xiaohan , Liu Shouyong , Lu Zhongwen , Xu Aiming , Qin Chao , Wang Zengjun
Published: February 2021

RNA-binding proteins (RBPs) play significant roles in various cancer types. However, the functions of RBPs have not been clarified in renal papillary cell carcinoma (pRCC). In this study, we identified 31 downregulated and 89 upregulated differentially expressed RBPs on the basis of the cancer genome atlas (TCGA) database and performed functional enrichment analyses. Subsequently, through univariate Cox, random survival forest, and multivariate Cox regression analysis, six RBPs of SNRPN, RRS1, INTS8, RBPMS2, IGF2BP3, and PIH1D2 were screened out, and the prognostic model was then established. Further analyses revealed that the high-risk group had poor overall survival. The area under the curve values were 0.87 and 0.75 at 3 years and 0.78 and 0.69 at 5 years in the training set and test set, respectively. We then plotted a nomogram on the basis of the six RBPs and tumor stage with the substantiation in the TCGA cohort. Moreover, we selected two intersectant RBPs and evaluate their biological effects by GSEA and predicted three drugs, including STOCK1N-28457, pyrimethamine, and trapidil by using the Connectivity Map. Our research provided a novel insight into pRCC and improved the determination of prognosis and individualized therapeutic strategies.
MSU-Net: Multi-Scale U-Net for 2D Medical Image Segmentation
Authors: Su Run , Zhang Deyun , Liu Jinhuai , Cheng Chuandong
Published: February 2021

Aiming at the limitation of the convolution kernel with a fixed receptive field and unknown prior to optimal network width in U-Net, multi-scale U-Net (MSU-Net) is proposed by us for medical image segmentation. First, multiple convolution sequence is used to extract more semantic features from the images. Second, the convolution kernel with different receptive fields is used to make features more diverse. The problem of unknown network width is alleviated by efficient integration of convolution kernel with different receptive fields. In addition, the multi-scale block is extended to other variants of the original U-Net to verify its universality. Five different medical image segmentation datasets are used to evaluate MSU-Net. A variety of imaging modalities are included in these datasets, such as electron microscopy, dermoscope, ultrasound, etc. Intersection over Union (IoU) of MSU-Net on each dataset are 0.771, 0.867, 0.708, 0.900, and 0.702, respectively. Experimental results show that MSU-Net achieves the best performance on different datasets. Our implementation is available athttps://github.com/CN-zdy/MSU_Net.
ORMDL2 Deficiency Potentiates the ORMDL3-Dependent Changes in Mast Cell Signaling
Authors: Bugajev Viktor , Halova Ivana , Demkova Livia , Cernohouzova Sara , Vavrova Petra , Mrkacek Michal , Utekal Pavol , Draberova Lubica , Kuchar Ladislav , Schuster Björn , Draber Petr
Published: February 2021

The systemic anaphylactic reaction is a life-threatening allergic response initiated by activated mast cells. Sphingolipids are an essential player in the development and attenuation of this response. De novo synthesis of sphingolipids in mammalian cells is inhibited by the family of three ORMDL proteins (ORMDL1, 2, and 3). However, the cell and tissue-specific functions of ORMDL proteins in mast cell signaling are poorly understood. This study aimed to determine cross-talk of ORMDL2 and ORMDL3 proteins in IgE-mediated responses. To this end, we prepared mice with whole-body knockout (KO) of Ormdl2 and/or Ormdl3 genes and studied their role in mast cell-dependent activation events in vitro and in vivo. We found that the absence of ORMDL3 in bone marrow-derived mast cells (BMMCs) increased the levels of cellular sphingolipids. Such an increase was further raised by simultaneous ORMDL2 deficiency, which alone had no effect on sphingolipid levels. Cells with double ORMDL2 and ORMDL3 KO exhibited increased intracellular levels of sphingosine-1-phosphate (S1P). Furthermore, we found that concurrent ORMDL2 and ORMDL3 deficiency increased IκB-α phosphorylation, degranulation, and production of IL-4, IL-6, and TNF-α cytokines in antigen-activated mast cells. Interestingly, the chemotaxis towards antigen was increased in all mutant cell types analyzed. Experiments in vivo showed that passive cutaneous anaphylaxis (PCA), which is initiated by mast cell activation, was increased only in ORMDL2,3 double KO mice, supporting our in vitro observations with mast cells. On the other hand, ORMDL3 KO and ORMDL2,3 double KO mice showed faster recovery from passive systemic anaphylaxis, which could be mediated by increased levels of blood S1P presented in such mice. Our findings demonstrate that Ormdl2 deficiency potentiates the ORMDL3-dependent changes in mast cell signaling.
Direct Infection of B Cells by Dengue Virus Modulates B Cell Responses in a Cambodian Pediatric Cohort
Authors: Upasani Vinit , Vo Hoa Thi My , Auerswald Heidi , Laurent Denis , Heng Sothy , Duong Veasna , Rodenhuis-Zybert Izabela A. , Dussart Philippe , Cantaert Tineke
Published: February 2021

Dengue is an acute viral disease caused by dengue virus (DENV), which is transmitted by Aedes mosquitoes. Symptoms of DENV infection range from inapparent to severe and can be life-threatening. DENV replicates in primary immune cells such as dendritic cells and macrophages, which contribute to the dissemination of the virus. Susceptibility of other immune cells such as B cells to direct infection by DENV and their subsequent response to infection is not well defined. In a cohort of 60 Cambodian children, we showed that B cells are susceptible to DENV infection. Moreover, we show that B cells can support viral replication of laboratory adapted and patient-derived DENV strains. B cells were permissive to DENV infection albeit low titers of infectious virions were released in cell supernatants CD300a, a phosphatidylserine receptor, was identified as a potential attachment factor or receptor for entry of DENV into B cells. In spite of expressing Fcγ-receptors, antibody-mediated enhancement of DENV infection was not observed in B cells in an in vitro model. Direct infection by DENV induced proliferation of B cells in dengue patients in vivo and plasmablast/plasma cell formation in vitro. To summarize, our results show that B cells are susceptible to direct infection by DENV via CD300a and the subsequent B cell responses could contribute to dengue pathogenesis.
Identification of a Novel Pattern Recognition Receptor DM9 Domain Containing Protein 4 as a Marker for Pro-Hemocyte of Pacific Oyster Crassostrea gigas
Authors: Jia Zhihao , Jiang Shuai , Wang Mengqiang , Wang Xiudan , Liu Yu , Lv Zhao , Song Xiaorui , Li Yiqun , Wang Lingling , Song Linsheng
Published: February 2021

DM9 refers to an uncharacterized protein domain that is originally discovered in Drosophila melanogaster. Two proteins with DM9 repeats have been recently identified from Pacific oyster Crassostrea gigas as mannose-specific binding pattern-recognition receptors (PRRs). In the present study, a novel member of DM9 domain containing protein (designated as CgDM9CP-4) was identified from C. gigas. CgDM9CP-4, about 16 kDa with only two tandem DM9 domains, was highly enriched in hemocytes and gill. The transcripts level of CgDM9CP-4 in circulating hemocytes were decreased after LPS, PGN and Vibrio splendidus stimulations. The recombinant protein of CgDM9CP-4 (rCgDM9CP-4) displayed a broad binding spectrum towards various pathogen-associated molecular patterns (PAMPs) (LPS, PGN, β-glucan and Mannose) and microorganisms (Staphylococcus aureus, Micrococcus luteus, V. splendidus, V. anguillarum, Escherichia coli, Pichia pastoris and Yarrowia lipolytica). CgDM9CP-4 was mostly expressed in gill and some of the hemocytes. Flow cytometry analysis demonstrated that the CgDM9CP-4-positive hemocytes accounted for 7.3% of the total hemocytes, and they were small in size and less in granularity. CgDM9CP-4 was highly expressed in non-phagocytes (~82% of total hemocytes). The reactive oxygen species (ROS) and the expression levels of cytokines in CgDM9CP-4-positive hemocytes were much lower than that in CgDM9CP-4-negative hemocytes. The mRNA expression level of CgDM9CP-4 in hemocytes was decreased after RNAi of hematopoietic-related factors (CgGATA, CgRunt, CgSCL, and CgNotch). In addition, CgDM9CP-4-positive cells were found to be much more abundant in hemocytes from gill than that from hemolymph, with most of them located in the gill filament. All these results suggested that CgDM9CP-4 was a novel member of PRR that expressed in undifferentiated pro-hemocytes to mediate immune recognition of pathogens.
The Role of Alpha 2 Macroglobulin in IgG-Aggregation and Chronic Activation of the Complement System in Patients With Chronic Lymphocytic Leukemia
Authors: Naseraldeen Naseba , Michelis Regina , Barhoum Masad , Chezar Judith , Tadmor Tamar , Aviv Ariel , Shvidel Lev , Litmanovich Adi , Shehadeh Mona , Stemer Galia , Shaoul Ety , Braester Andrei
Published: February 2021

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in the western world. One of the treatments offered for CLL is immunotherapy. These treatments activate various cellular and biochemical mechanisms, using the complement system. Recently it was shown that the complement system in CLL patients is persistently activated at a low level through the classical pathway (CP). The mechanism of chronic CP activation involves the formation of IgG-hexamers (IgG-aggregates). According to recent studies, formation of ordered IgG-hexamers occurs on cell surfaces via specific interactions between Fc regions of the IgG monomers, which occur after antigen binding. The present study investigated the formation of IgG-hexamers in CLL patients and normal (non-malignant) controls (NC), their ability to activate complement, their incidence as cell-free and cell-bound forms and the identity of the antigen causing their formation. Sera from 30 patients and 12 NC were used for separation of IgG- aggregates. The obtained IgG- aggregates were measured and used for assessment of CP activation. For evaluation of the presence of IgG- aggregates on blood cells, whole blood samples were stained and assessed by flow cytometry. Serum levels of IgG- aggregates were higher in CLL and they activated the complement system to a higher extent than in NC. Alpha 2 macroglobulin (A2M) was identified as the antigen causing the hexamerization/aggregation of IgG, and was found to be part of the hexamer structure by mass spectrometry, Western blot and flow cytometry analysis. The presence of A2M-IgG-hexamers on B-cells suggests that it may be formed on B cells surface and then be detached to become cell-free. Alternatively, it may form in the plasma and then attach to the cell surface. The exact time course of A2M-IgG-hexamers formation in CLL should be further studied. The results in this study may be useful for improvement of current immunotherapy regimens.
Mobilized Multipotent Hematopoietic Progenitors Promote Expansion and Survival of Allogeneic Tregs and Protect Against Graft Versus Host Disease
Authors: D’Aveni Maud , Notarantonio Anne-Béatrice , Agbogan Viviane A. , Bertrand Allan , Fouquet Guillemette , Gastineau Pauline , Garfa-Traoré Meriem , De Carvalho Marcelo , Hermine Olivier , Rubio Marie-Thérèse , Zavala Flora
Published: February 2021

Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) is routinely performed with peripheral blood stem cells (PBSCs) mobilized by injection of G-CSF, a growth factor which not only modulates normal hematopoiesis but also induces diverse immature regulatory cells. Based on our previous evidence that G-CSF-mobilized multipotent hematopoietic progenitors (MPP) can increase survival and proliferation of natural regulatory T cells (Tregs) in autoimmune disorders, we addressed the question how these cells come into play in mice and humans in an alloimmune setting. Using a C57BL/6 mouse model, we demonstrate that mobilized MPP enhance the immunosuppressant effect exerted by Tregs, against alloreactive T lymphocytes, both in vitro and in vivo. They do so by migrating to sites of allopriming, interacting with donor Tregs and increasing their numbers, thus reducing the lethality of graft-versus-host disease (GVHD). Protection correlates likewise with increased allospecific Treg counts. Furthermore, we provide evidence for a phenotypically similar MPP population in humans, where it shares the capacity to promote selective Treg expansion in vitro. We postulate that G-CSF-mobilized MPPs might become a valuable cellular therapy to expand donor Tregs in vivo and prevent GVHD, thereby making allo-HSCT safer for the treatment of leukemia patients.
Differential Longevity of Memory CD4 and CD8 T Cells in a Cohort of the Mothers With a History of ZIKV Infection and Their Children
Authors: Badolato-Corrêa Jessica , Carvalho Fabiana Rabe , Paiva Iury Amancio , Familiar-Macedo Débora , Dias Helver Gonçalves , Pauvolid-Corrêa Alex , Fernandes-Santos Caroline , Lima Monique da Rocha Queiroz , Gandini Mariana , Silva Andréa Alice , Baeta Cavalcanti Silvia Maria , de Oliveira Solange Artimos , de Oliveira Vianna Renata Artimos , de Azeredo Elzinandes Leal , Cardoso Claudete Aparecida Araújo , Grifoni Alba , Sette Alessandro , Weiskopf Daniela , de-Oliveira-Pinto Luzia Maria
Published: February 2021

Background:Zika virus (ZIKV) infection causes for mild and self-limiting disease in healthy adults. In newborns, it can occasionally lead to a spectrum of malformations, the congenital Zika syndrome (CZS). Thus, little is known if mothers and babies with a history of ZIKV infection were able to develop long-lasting T-cell immunity. To these issues, we measure the prevalence of ZIKV T-cell immunity in a cohort of mothers infected to the ZIKV during pregnancy in the 2016–2017 Zika outbreak, who gave birth to infants affected by neurological complications or asymptomatic ones.

Results:Twenty-one mothers and 18 children were tested for IFN-γ ELISpot and T-cell responses for flow cytometry assays in response to CD4 ZIKV and CD8 ZIKV megapools (CD4 ZIKV MP and CD8 ZIKV MP). IFN-γ ELISpot responses to ZIKV MPs showed an increased CD4 and CD8 T-cell responses in mothers compared to children. The degranulation activity and IFN-γ-producing CD4 T cells were detected in most mothers, and children, while in CD8 T-cells, low responses were detected in these study groups. The total Temra T cell subset is enriched for IFN-γ+ CD4 T cells after stimulation of CD4 ZIKV MP.

Conclusion:Donors with a history of ZIKV infection demonstrated long-term CD4 T cell immunity to ZIKV CD4 MP. However, the same was not observed in CD8 T cells with the ZIKV CD8 MP. One possibility is that the cytotoxic and pro-inflammatory activities of CD8 T cells are markedly demonstrated in the early stages of infection, but less detected in the disease resolution phase, when the virus has already been eliminated. The responses of mothers' T cells to ZIKV MPs do not appear to be related to their children's clinical outcome. There was also no marked difference in the T cell responses to ZIKV MP between children affected or not with CZS. These data still need to be investigated, including the evaluation of the response of CD8 T cells to other ZIKV peptides.
The Immunopathology of COVID-19 and the Cannabis Paradigm
Authors: Paland Nicole , Pechkovsky Antonina , Aswad Miran , Hamza Haya , Popov Tania , Shahar Eduardo , Louria-Hayon Igal
Published: February 2021

Coronavirus disease-19 caused by the novel RNA betacoronavirus SARS-CoV2 has first emerged in Wuhan, China in December 2019, and since then developed into a worldwide pandemic with >99 million people afflicted and >2.1 million fatal outcomes as of 24th January 2021. SARS-CoV2 targets the lower respiratory tract system leading to pneumonia with fever, cough, and dyspnea. Most patients develop only mild symptoms. However, a certain percentage develop severe symptoms with dyspnea, hypoxia, and lung involvement which can further progress to a critical stage where respiratory support due to respiratory failure is required. Most of the COVID-19 symptoms are related to hyperinflammation as seen in cytokine release syndrome and it is believed that fatalities are due to a COVID-19 related cytokine storm. Treatments with anti-inflammatory or anti-viral drugs are still in clinical trials or could not reduce mortality. This makes it necessary to develop novel anti-inflammatory therapies. Recently, the therapeutic potential of phytocannabinoids, the unique active compounds of the cannabis plant, has been discovered in the area of immunology. Phytocannabinoids are a group of terpenophenolic compounds which biological functions are conveyed by their interactions with the endocannabinoid system in humans. Here, we explore the anti-inflammatory function of cannabinoids in relation to inflammatory events that happen during severe COVID-19 disease, and how cannabinoids might help to prevent the progression from mild to severe disease.
Update on Infections in Primary Antibody Deficiencies
Authors: Demirdag Yesim Yilmaz , Gupta Sudhir
Published: February 2021

Bacterial respiratory tract infections are the hallmark of primary antibody deficiencies (PADs). Because they are also among the most common infections in healthy individuals, PADs are usually overlooked in these patients. Careful evaluation of the history, including frequency, chronicity, and presence of other infections, would help suspect PADs. This review will focus on infections in relatively common PADs, discussing diagnostic challenges, and some management strategies to prevent infections.
Case Report: Mastocytosis: The Long Road to Diagnosis
Authors: Rama Tiago Azenha , Martins Diana , Gomes Nuno , Pinheiro Jorge , Nogueira Ana , Delgado Luís , Plácido José Luís , Coimbra Alice
Published: February 2021

Mastocytosis is a heterogeneous group of disorders characterized by expansion and accumulation of clonal mast cells. Patients mainly present with either cutaneous lesions, anaphylaxis, or both. Its low prevalence and unusual features often hinder its diagnosis for several years. We report the case of an 18-year-old male who was referred to our department with a long-standing history of atypical skin lesions, allergic rhinitis, exercise-induced bronchoconstriction and what was believed to be food-related flushing and anaphylaxis, that was later diagnosed with mastocytosis. This case illustrates the need to consider investigating for mastocytosis when recurrent anaphylaxis is present, especially in the presence of atypical skin lesions, even if normal serum basal tryptase levels and allergic sensitization are present.
Dual Antiretroviral Therapy—All Quiet Beneath the Surface?
Authors: van Welzen Berend J. , Oomen Patrick G. A. , Hoepelman Andy I. M.
Published: February 2021

Infection with the human immunodeficiency virus (HIV) is characterized by progressive depletion of CD4+ lymphocytes cells as a result of chronic immune activation. Next to the decreases in the number of CD4+ cells which leads to opportunistic infections, HIV-related immune activation is associated with several prevalent comorbidities in the HIV-positive population such as cardiovascular and bone disease. Traditionally, combination antiretroviral therapy (cART) consists of three drugs with activity against HIV and is highly effective in diminishing the degree of immune activation. Over the years, questions were raised whether virological suppression could also be achieved with fewer antiretroviral drugs, i.e., dual- or even monotherapy. This is an intriguing question considering the fact that antiretroviral drugs should be used lifelong and their use could also induce cardiovascular and bone disease. Therefore, the equilibrium between drug-induced toxicity and immune activation related comorbidity is delicate. Recently, two large clinical trials evaluating two-drug cART showed non-inferiority with respect to virological outcomes when compared to triple-drug regimens. This led to adoption of dual antiretroviral therapy in current HIV treatment guidelines. However, it is largely unknown whether dual therapy is also able to suppress immune activation to the same degree as triple therapy. This poses a risk for an imbalance in the delicate equilibrium. This mini review gives an overview of the current available evidence concerning immune activation in the setting of cART with less than three antiretroviral drugs.
Improving Regional Model Skills During Typhoon Events: A Case Study for Super Typhoon Lingling Over the Northwest Pacific Ocean
Authors: Li Delei , Staneva Joanna , Bidlot Jean-Raymond , Grayek Sebastian , Zhu Yuchao , Yin Baoshu
Published: February 2021

The ability of forecasting systems to simulate tropical cyclones is still insufficient, and currently, there is an increased interest in improving model performance for intense tropical cyclones. In this study, the impact of reducing surface drag at high wind speeds on modeling wind and wave conditions during the super Typhoon Lingling event over the northwest Pacific Ocean in 2019 is investigated. The model response with respect to the parameterization for momentum exchange at the ocean surface is demonstrated using a fully coupled regional atmosphere model (the Consortium for Small-Scale Modeling-Climate Limited-area Modeling, CCLM) and a wind wave model (WAM). The active two-way coupling between the atmosphere and ocean waves model is enabled through the introduction of sea state-dependent surface drag into the CCLM and updated winds into the WAM. The momentum exchange with the sea surface is modeled via the dependency of the roughness length (Z0) on the surface stress itself and, when applicable, on the wind speed. Several high-resolution runs are performed using one-way or two-way fully coupled regional atmosphere-wave (CCLM-WAM) models. The model simulations are assessed against the best track data as well as against buoy and satellite observations. The results show that the spectral nudging technique can improve the model’s ability to capture the large-scale circulation, track and intensity of Typhoon Lingling at regional scales. Under the precondition of large-scale constraining, the two-way coupling simulation with the proposed new roughness parameterization performs much better than the simulations used in older studies in capturing the maximum wind speed of Typhoon Lingling due to the reduced drag at extreme wind conditions for the new Z0.
Water- and Base-Extractable Organic Matter in Sediments From Lower Yangtze River–Estuary–East China Sea Continuum: Insight Into Accumulation of Organic Carbon in the River-Dominated Margin
Authors: Han Lulu , Wang Yinghui , Xu Yunping , Wang Yasong , Zheng Yiling , Wu Jianqiang
Published: February 2021

The burial of organic carbon (OC) in the river-dominated margin plays an important role in global carbon cycle, but its accumulation mechanism is not well understood. Here, we examined the concentration and distribution of water-extractable organic matter (WEOM) and base-extractable organic matter (BEOM) in surface sediments from the lower Yangtze River, estuary, and the East China Sea. Chemical characteristics of the WEOM and BEOM were described by multiple ultraviolet-visible and fluorescence spectral indicators. Concentrations of both WEOM and BEOM showed significant correlations with sediment grain size, suggesting that mineral surface area is a key factor for OC loadings on sediments. Three components (C1, C2, and C3) extracted from fluorescence excitation emission matrices-parallel factor analysis were assigned as terrigenous humic-like substance, mixed terrigenous/aquatic humic-like substance, and microbial protein-like substance, respectively. From the lower Yangtze River to the East China Sea, the C1%, specific UV absorbance at 254 nm (SUVA254), and humification index (HIX) of the WEOM decreased, while the C3%, fluorescence index (FI), and biological index (BIX) of the WEOM increased. This suggested the loss of terrigenous OC and addition of microbial OC in the WEOM. While for BEOM, the overall increase of C1% and HIX and the decrease of C3% and FI suggested selective removal of microbial OC and preferential preservation of terrigenous OC. Our study demonstrates complex behaviors of sediment organic matter (OM) during the land-to-sea transport that is largely controlled by the binding strength of OM–sediment association, and that the formation of BEOM is an important pathway for accumulation of terrigenous OM in the river-dominated margin.
Mesophotic Coral Ecosystems of the Great Barrier Reef Are Understudied and Underexplored
Authors: Eyal Gal , Laverick Jack H. , Bongaerts Pim , Levy Oren , Pandolfi John M.
Published: February 2021

Mesophotic coral ecosystems (MCEs) are characterized by the presence of photosynthetically active organisms such as corals and algae, and associated communities at depths ranging from 30 to 150 m in tropical and subtropical regions. Due to the increased awareness of the potential importance of these reefs as an integral part of coral reef ecosystems (i.e., deep reef refuge, specialized biodiversity, transition zone between shallow and deep-sea environments, and recreational and intrinsic values), interest from the scientific community has grown around the world over the last two decades. Several nations have already made management declarations and started to extend marine protected areas and fishery management to MCEs. The estimated area of Australian MCEs is likely equivalent to that of shallow reef ecosystems down to 30 m; however, Australian MCEs attract limited research effort compared to other major coral reef regions around the world. In this perspective, we briefly explore the reasons for this scarcity of research on mesophotic ecosystems of the Great Barrier Reef (GBR) of Australia (e.g., strict diving regulations, new researchers’ involvement, and logistics and cost). At present, research efforts on the mesophotic ecosystems of the GBR are in decline and if this trajectory is maintained, the global disparity in knowledge between MCEs near Australia and those from the other main coral reef regions worldwide will sharpen deeply. We call for action from the research community, grant agencies, and decision-makers toward a wider understanding of these important ecosystems in Australia.
Abiotic and Human Drivers of Reef Habitat Complexity Throughout the Main Hawaiian Islands
Authors: Asner Gregory P. , Vaughn Nicholas R. , Foo Shawna A. , Shafron Ethan , Heckler Joseph , Martin Roberta E.
Published: February 2021

Reef rugosity, a metric of three-dimensional habitat complexity, is a central determinant of reef condition and multi-trophic occupancy including corals, fishes and invertebrates. As a result, spatially explicit information on reef rugosity is needed for conservation and management activities ranging from fisheries to coral protection and restoration. Across archipelagos comprising islands of varying geologic stage and age, rugosity naturally varies at multiple spatial scales based on island emergence, subsidence, and erosion. Reef rugosity may also be changing due to human impacts on corals such as marine heatwaves and nearshore coastal development. Using a new high-resolution, large-area mapping technique based on airborne imaging spectroscopy, we mapped the rugosity of reefs to 22 m depth throughout the eight Main Hawaiian Islands. We quantified inter- and intra-island variation in reef rugosity at fine (2 m) and coarse (6 m) spatial resolutions, and tested potential abiotic and human drivers of rugosity patterns. We found that water depth and reef slope remain the dominant drivers of fine- and coarse-scale rugosity, but nearshore development is a secondary driver of rugosity. Our results and maps can be used by fisheries management and reef conservations to track geologic versus human impacts on reefs, design effective marine managed areas, and execute activities to improve reef resilience.