bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body
Authors: Cristofori Fernanda , Dargenio Vanessa Nadia , Dargenio Costantino , Miniello Vito Leonardo , Barone Michele , Francavilla Ruggiero
Published: February 2021

Hosting millions of microorganisms, the digestive tract is the primary and most important part of bacterial colonization. On one side, in cases of opportunistic invasion, the abundant bacterial population inside intestinal tissues may face potential health problems such as inflammation and infections. Therefore, the immune system has evolved to sustain the host–microbiota symbiotic relationship. On the other hand, to maintain host immune homeostasis, the intestinal microflora often exerts an immunoregulatory function that cannot be ignored. A field of great interest is the association of either microbiota or probiotics with the immune system concerning clinical uses. This microbial community regulates some of the host’s metabolic and physiological functions and drives early-life immune system maturation, contributing to their homeostasis throughout life. Changes in gut microbiota can occur through modification in function, composition (dysbiosis), or microbiota–host interplays. Studies on animals and humans show that probiotics can have a pivotal effect on the modulation of immune and inflammatory mechanisms; however, the precise mechanisms have not yet been well defined. Diet, age, BMI (body mass index), medications, and stress may confound the benefits of probiotic intake. In addition to host gut functions (permeability and physiology), all these agents have profound implications for the gut microbiome composition. The use of probiotics could improve the gut microbial population, increase mucus-secretion, and prevent the destruction of tight junction proteins by decreasing the number of lipopolysaccharides (LPSs). When LPS binds endothelial cells to toll-like receptors (TLR 2, 4), dendritic cells and macrophage cells are activated, and inflammatory markers are increased. Furthermore, a decrease in gut dysbiosis and intestinal leakage after probiotic therapy may minimize the development of inflammatory biomarkers and blunt unnecessary activation of the immune system. In turn, probiotics improve the differentiation of T-cells against Th2 and development of Th2 cytokines such as IL-4 and IL-10. The present narrative review explores the interactions between gut microflora/probiotics and the immune system starting from the general perspective of a biological plausibility to get to the in vitro and in vivo demonstrations of a probiotic-based approach up to the possible uses for novel therapeutic strategies.
Peptidomes and Structures Illustrate Two Distinguishing Mechanisms of Alternating the Peptide Plasticity Caused by Swine MHC Class I Micropolymorphism
Authors: Wei Xiaohui , Wang Song , Li Zhuolin , Li Zibin , Qu Zehui , Wang Suqiu , Zou Baohua , Liang Ruiying , Xia Chun , Zhang Nianzhi
Published: February 2021

The micropolymorphism of major histocompatibility complex class I (MHC-I) can greatly alter the plasticity of peptide presentation, but elucidating the underlying mechanism remains a challenge. Here we investigated the impact of the micropolymorphism on peptide presentation of swine MHC-I (termed swine leukocyte antigen class I, SLA-I) molecules via immunopeptidomes that were determined by our newly developed random peptide library combined with the mass spectrometry (MS) de novo sequencing method (termed RPLD–MS) and the corresponding crystal structures. The immunopeptidomes of SLA-1*04:01, SLA-1*13:01, and their mutants showed that mutations of residues 156 and 99 could expand and narrow the ranges of peptides presented by SLA-I molecules, respectively. R156A mutation of SLA-1*04:01 altered the charge properties and enlarged the volume size of pocket D, which eliminated the harsh restriction to accommodate the third (P3) anchor residue of the peptide and expanded the peptide binding scope. Compared with 99Tyr of SLA-1*0401, 99Phe of SLA-1*13:01 could not form a conservative hydrogen bond with the backbone of the P3 residues, leading to fewer changes in the pocket properties but a significant decrease in quantitative of immunopeptidomes. This absent force could be compensated by the salt bridge formed by P1-E and 170Arg. These data illustrate two distinguishing manners that show how micropolymorphism alters the peptide-binding plasticity of SLA-I alleles, verifying the sensitivity and accuracy of the RPLD-MS method for determining the peptide binding characteristics of MHC-I in vitro and helping to more accurately predict and identify MHC-I restricted epitopes.
The Roles of Immunoregulatory Networks in Severe Drug Hypersensitivity
Authors: Hsu Yun-Shiuan Olivia , Lu Kun-Lin , Fu Yun , Wang Chuang-Wei , Lu Chun-Wei , Lin Yu-Fen , Chang Wen-Cheng , Yeh Kun-Yun , Hung Shuen-Iu , Chung Wen-Hung , Chen Chun-Bing
Published: February 2021

The immunomodulatory effects of regulatory T cells (Tregs) and co-signaling receptors have gained much attention, as they help balance immunogenic and immunotolerant responses that may be disrupted in autoimmune and infectious diseases. Drug hypersensitivity has a myriad of manifestations, which ranges from the mild maculopapular exanthema to the severe Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS). While studies have identified high-risk human leukocyte antigen (HLA) allotypes, the presence of the HLA allotype at risk is not sufficient to elicit drug hypersensitivity. Recent studies have suggested that insufficient regulation by Tregs may play a role in severe hypersensitivity reactions. Furthermore, immune checkpoint inhibitors, such as anti-CTLA-4 or anti-PD-1, in cancer treatment also induce hypersensitivity reactions including SJS/TEN and DRESS/DIHS. Taken together, mechanisms involving both Tregs as well as coinhibitory and costimulatory receptors may be crucial in the pathogenesis of drug hypersensitivity. In this review, we summarize the currently implicated roles of co-signaling receptors and Tregs in delayed-type drug hypersensitivity in the hope of identifying potential pharmacologic targets.
FLI1 Induces Megakaryopoiesis Gene Expression Through WAS/WIP-Dependent and Independent Mechanisms; Implications for Wiskott-Aldrich Syndrome
Authors: Wang Chunlin , Sample Klarke M. , Gajendran Babu , Kapranov Philipp , Liu Wuling , Hu Anling , Zacksenhaus Eldad , Li Yanmei , Hao Xiaojiang , Ben-David Yaacov
Published: February 2021

Wiskott–Aldrich Syndrome, WAS/WAVE, is a rare, X-linked immune-deficiency disease caused by mutations in the WAS gene, which together with its homolog, N-WASP, regulates actin cytoskeleton remodeling and cell motility. WAS patients suffer from microthrombocytopenia, characterized by a diminished number and size of platelets, though the underlying mechanism is not fully understood. Here, we identified FLI1 as a direct transcriptional regulator of WAS and its binding partner WIP. Depletion of either WAS or WIP in human erythroleukemic cells accelerated cell proliferation, suggesting tumor suppressor function of both genes in leukemia. Depletion of WAS/WIP also led to a significant reduction in the percentage of CD41 and CD61 positive cells, which mark committed megakaryocytes. RNAseq analysis revealed common changes in megakaryocytic gene expression following FLI1 or WASP knockdown. However, in contrast to FLI1, WASP depletion did not alter expression of late-stage platelet-inducing genes. N-WASP was not regulated by FLI1, yet its silencing also reduced the percentage of CD41+ and CD61+ megakaryocytes. Moreover, combined knockdown of WASP and N-WASP further suppressed megakaryocyte differentiation, indicating a major cooperation of these related genes in controlling megakaryocytic cell fate. However, unlike WASP/WIP, N-WASP loss suppressed leukemic cell proliferation. WASP, WIP and N-WASP depletion led to induction of FLI1 expression, mediated by GATA1, and this may mitigate the severity of platelet deficiency in WAS patients. Together, these results uncover a crucial role for FLI1 in megakaryocyte differentiation, implicating this transcription factor in regulating microthrombocytopenia associated with Wiskott–Aldrich syndrome.
Icaritin Induces Anti-tumor Immune Responses in Hepatocellular Carcinoma by Inhibiting Splenic Myeloid-Derived Suppressor Cell Generation
Authors: Tao Huimin , Liu Mingyu , Wang Yuan , Luo Shufeng , Xu Yongquan , Ye Bin , Zheng Limin , Meng Kun , Li Lian
Published: February 2021

Recent studies have demonstrated that splenic extramedullary hematopoiesis (EMH) is an important mechanism for the accumulation of myeloid-derived suppressor cells (MDSCs) in tumor tissues, and thus contributes to disease progression. Icaritin, a prenylflavonoid derivative from plants of the Epimedium genus, has been implicated as a novel immune-modulator that could prolong the survival of hepatocellular carcinoma (HCC) patients. However, it is unclear whether icaritin achieves its anti-tumor effects via the regulation of MDSCs generated by EMH in HCC. Here, we investigated the anti-tumor potential of icaritin and its mechanism of action in murine HCC. Icaritin suppressed tumor progression and significantly prolonged the survival of mice-bearing orthotopic and subcutaneous HCC tumors. Rather than exerting direct cytotoxic activity against tumor cells, icaritin significantly reduced the accumulation and activation of tumoral and splenic MDSCs, and increased the number and activity of cytotoxic T cells. Mechanistically, icaritin downregulates the tumor-associated splenic EMH, thereby reducing the generation and activation of MDSCs. The inhibitory effects of icaritin on human MDSCs in vitro were verified in short-term culture with cord-blood derived hematopoietic precursors. Furthermore, icaritin synergistically enhanced the therapeutic efficacy of immune checkpoint blockade therapy in HCC mice. These findings revealed that icaritin dampens tumoral immunosuppression to elicit anti-tumor immune responses by preventing MDSC generation via the attenuation of EMH. Thus, icaritin may serve as a novel adjuvant or even a stand-alone therapeutic agent for the effective treatment of HCC.
Effects of Different Chromium Compounds on Hematology and Inflammatory Cytokines in Rats Fed High-Fat Diet
Authors: Dworzański Wojciech , Sembratowicz Iwona , Cholewińska Ewelina , Tutaj Krzysztof , Fotschki Bartosz , Juśkiewicz Jerzy , Ognik Katarzyna
Published: February 2021

The aim of the study was to determine how a high-fat diet supplemented with various forms of chromium affects hematological and immune parameters of the blood of rats. The rats received a standard diet or a high-fat diet supplemented with chromium at 0.3 mg/kg body weight (BW) in the form of chromium(III) picolinate, chromium(III)-methionine or nano-sized chromium. Selected hematological parameters were determined in the blood of the rats, including total white blood cell (WBC) count, leukogram, red blood cell (RBC) count, hemoglobin level (HGB), hematocrit (HCT), platelet count (PLT) and platelet percentage (PCT), as well as immune parameters: levels of immunoglobulins A and E (IgA and IgE), interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor α (TNF-α); activity of ceruloplasmin (Cp); and levels of caspase 3 and 8 (Casp3 and Casp8). Feeding rats a high-fat diet increased blood markers of induction of inflammation, ie pro-inflammatory cytokines IL-6 and TNF-α, and also significantly increased IgE. The diet had no effect on the blood count, except for an increase in the number of neutrophils. The chromium compounds tested, particularly Cr-Met and Cr-NPs, stimulated the immune system of the rats, as indicated by increased concentrations of IgA, IgE, IL-2, IL-6, TNF-α, and Cp. Given the increase in inflammatory mediators induced by chromium, it should not be used to mitigate the effects of a high-fat diet. Moreover, chromium picolinate and chromium nanoparticles were shown to increase the content of caspase 3 and 8 in the blood of rats, which indicates a pro-apoptotic effect. The effects of the use of chromium nanoparticles include reductions in the WBC count and in the thrombocyte count (leuko- and thrombopenia). Taking account these data the use of chromium as dietary supplement should be reconsidered.
Monocyte Subset Recruitment Marker Profile Is Inversely Associated With Blood ApoA1 Levels
Authors: Patel Vyoma K. , Williams Helen , Li Stephen C. H. , Fletcher John P. , Medbury Heather J.
Published: February 2021

Dyslipidemia promotes development of the atherosclerotic plaques that characterise cardiovascular disease. Plaque progression requires the influx of monocytes into the vessel wall, but whether dyslipidemia is associated with an increased potential of monocytes to extravasate is largely unknown. Here (using flow cytometry) we examined recruitment marker expression on monocytes from generally healthy individuals who differed in lipid profile. Comparisons were made between monocyte subsets, participants and relative to participants’ lipid levels. Monocyte subsets differed significantly in their expression of recruitment markers, with highest expression being on either the classical or non-classical subsets. However, these inter-subset differences were largely overshadowed by considerable inter-participant differences with some participants having higher levels of recruitment markers on all three monocyte subsets. Furthermore, when the expression of one recruitment marker was high, so too was that of most of the other markers, with substantial correlations evident between the markers. The inter-participant differences were explained by lipid levels. Most notably, there was a significant inverse correlation for most markers with ApoA1 levels. Our results indicate that dyslipidemia, in particular low levels of ApoA1, is associated with an increased potential of all monocyte subsets to extravasate, and to do so using a wider repertoire of recruitment markers than currently appreciated.
Resident Innate Immune Cells in the Cornea
Authors: Liu Jun , Li Zhijie
Published: February 2021

The cornea is a special interface between the internal ocular tissue and the external environment that provides a powerful chemical, physical, and biological barrier against the invasion of harmful substances and pathogenic microbes. This protective effect is determined by the unique anatomical structure and cellular composition of the cornea, especially its locally resident innate immune cells, such as Langerhans cells (LCs), mast cells (MCs), macrophages, γδ T lymphocytes, and innate lymphoid cells. Recent studies have demonstrated the importance of these immune cells in terms of producing different cytokines and other growth factors in corneal homeostasis and its pathologic conditions. This review paper briefly describes the latest information on these resident immune cells by specifically analyzing research from our laboratory.
A Large-Scale Bank of Organ Donor Bone Marrow and Matched Mesenchymal Stem Cells for Promoting Immunomodulation and Transplant Tolerance
Authors: Johnstone Brian H. , Messner Franka , Brandacher Gerald , Woods Erik J.
Published: February 2021

Induction of immune tolerance for solid organ and vascular composite allografts is the Holy Grail for transplantation medicine. This would obviate the need for life-long immunosuppression which is associated with serious adverse outcomes, such as infections, cancers, and renal failure. Currently the most promising means of tolerance induction is through establishing a mixed chimeric state by transplantation of donor hematopoietic stem cells; however, with the exception of living donor renal transplantation, the mixed chimerism approach has not achieved durable immune tolerance on a large scale in preclinical or clinical trials with other solid organs or vascular composite allotransplants (VCA). Ossium Health has established a bank of cryopreserved bone marrow (BM), termed “hematopoietic progenitor cell (HPC), Marrow,” recovered from deceased organ donor vertebral bodies. This new source for hematopoietic cell transplant will be a valuable resource for treating hematological malignancies as well as for inducing transplant tolerance. In addition, we have discovered and developed a large source of mesenchymal stem (stromal) cells (MSC) tightly associated with the vertebral body bone fragment byproduct of the HPC, Marrow recovery process. Thus, these vertebral bone adherent MSC (vBA-MSC) are matched to the banked BM obtained from each donor, as opposed to third-party MSC, which enhances safety and potentially efficacy. Isolation and characterization of vBA-MSC from over 30 donors has demonstrated that the cells are no different than traditional BM-MSC; however, their abundance is >1,000-fold higher than obtainable from living donor BM aspirates. Based on our own unpublished data as well as reports published by others, MSC facilitate chimerism, especially at limiting hematopoietic stem and progenitor cell (HSPC) numbers and increase safety by controlling and/or preventing graft-vs.-host-disease (GvHD). Thus, vBA-MSC have the potential to facilitate mixed chimerism, promote complementary peripheral immunomodulatory functions and increase safety of BM infusions. Both HPC, Marrow and vBA-MSC have potential use in current VCA and solid organ transplant (SOT) tolerance clinical protocols that are amenable to “delayed tolerance.” Current trials with HPC, Marrow are planned with subsequent phases to include vBA-MSC for tolerance of both VCA and SOT.
Microbiome or Infections: Amyloid-Containing Biofilms as a Trigger for Complex Human Diseases
Authors: Miller Amanda L. , Bessho Shingo , Grando Kaitlyn , Tükel Çagla
Published: February 2021

The human microbiota is the community of microorganisms that live upon or within their human host. The microbiota consists of various microorganisms including bacteria, fungi, viruses, and archaea; the gut microbiota is comprised mostly of bacteria. Many bacterial species within the gut microbiome grow as biofilms, which are multicellular communities embedded in an extracellular matrix. Studies have shown that the relative abundances of bacterial species, and therefore biofilms and bacterial byproducts, change during progression of a variety of human diseases including gastrointestinal, autoimmune, neurodegenerative, and cancer. Studies have shown the location and proximity of the biofilms within the gastrointestinal tract might impact disease outcome. Gram-negative enteric bacteria secrete the amyloid curli, which makes up as much as 85% of the extracellular matrix of enteric biofilms. Curli mediates cell-cell attachment and attachment to various surfaces including extracellular matrix components such as fibronectin and laminin. Structurally, curli is strikingly similar to pathological and immunomodulatory human amyloids such as amyloid-β, which has been implicated in Alzheimer's disease, α-synuclein, which is involved in Parkinson's disease, and serum amyloid A, which is secreted during the acute phase of inflammation. The immune system recognizes both bacterial amyloid curli and human amyloids utilizing the same receptors, so curli also induces inflammation. Moreover, recent work indicates that curli can participate in the self-assembly process of pathological human amyloids. Curli is found within biofilms of commensal enteric bacteria as well as invasive pathogens; therefore, evidence suggests that curli contributes to complex human diseases. In this review, we summarize the recent findings on how bacterial biofilms containing curli participate in the pathological and immunological processes in gastrointestinal diseases, systemic autoimmune diseases, and neurodegenerative diseases.
Initialization of WRF Model Simulations With Sentinel-1 Wind Speed for Severe Weather Events
Authors: Tiesi Alessandro , Pucillo Arturo , Bonaldo Davide , Ricchi Antonio , Carniel Sandro , Miglietta Mario Marcello
Published: February 2021

The model initialization with high-resolution SAR wind data provided by the Sentinel-1 mission and its impact on the meteorological model WRF-ARW simulations is discussed. The activity is performed within the Horizon 2020 CEASELESS project, focusing on one of the target areas, the northern Adriatic Sea (northern-central Mediterranean). The Sentinel-1 SAR wind is ingested into LAPS, a numerical system developed at NOAA, specifically designed for data analysis and nowcasting issues, since it has the advantage of being faster and less computational demanding than advanced data assimilation methods. Here, LAPS analyses are used to perform a smarter initialization of the WRF-ARW model simulations than using simply global model fields. The impact of the Sentinel-1 SAR wind on the model simulations is evaluated for twenty cases, ranging through several atmospheric conditions occurring in different seasons of the years 2014–2018. For each case study, a reference WRF-ARW simulation is forced with GFS analysis and forecasts used as initial and boundary conditions, respectively. Additional model runs are initialized with the LAPS analyses, which include the information of Sentinel-1 SAR wind, METAR data and the SEVIRI/MSG (Eumetsat) brightness temperature. A statistical evaluation of the WRF-ARW simulations is performed versus an independent set of surface records, provided by the Friuli Venezia Giulia regional station network (northeastern Italy), and METAR data. The comparison is performed for 10 m wind, 2 m air and dew point temperature. The results show a positive, albeit modest, impact on the WRF model simulations initialized with the LAPS analyses. The initialization with the Sentinel-1 SAR wind show benefits for all surface variables. Finally, a Mediterranean tropical-like cyclone (Medicane), occurred in the Ionian Sea in November 2017, is considered in order to show how the use of Sentinel wind data can contribute to a better analysis and simulation of severe weather episodes in the Mediterranean. The improvement in the simulation of the pressure minimum location is remarkable.
It’s Not the Destination, It’s the Journey: Multispecies Model Ensembles for Ecosystem Approaches to Fisheries Management
Authors: Reum Jonathan C. P. , Townsend Howard , Gaichas Sarah , Sagarese Skyler , Kaplan Isaac C. , Grüss Arnaud
Published: February 2021

As ecosystem-based fisheries management becomes more ingrained into the way fisheries agencies do business, a need for ecosystem and multispecies models arises. Yet ecosystems are complex, and model uncertainty can be large. Model ensembles have historically been used in other disciplines to address model uncertainty. To understand the benefits and limitations of multispecies model ensembles (MMEs), cases where they have been used in the United States to address fisheries management issues are reviewed. The cases include: (1) development of ecological reference points for Atlantic Menhaden, (2) the creation of time series to relate harmful algal blooms to grouper mortality in the Gulf of Mexico, and (3) fostering understanding of the role of forage fish in the California Current. Each case study briefly reviews the management issue, the models used and model synthesis approach taken, and the outcomes and lessons learned from the application of MMEs. Major conclusions drawn from these studies highlight how the act of developing an ensemble model suite can improve the credibility of multispecies models, how qualitative synthesis of projections can advance system understanding and build confidence in the absence of quantitative treatments, and how involving a diverse set of stakeholders early is useful for ensuring the utility of the models and ensemble. Procedures for review and uptake of information from single-species stock assessment models are well established, but the absence of well-defined procedures for MMEs in many fishery management decision-making bodies poses a major obstacle. The benefits and issues identified here should help accelerate the design, implementation, and utility of MMEs in applied fisheries contexts.
Bioluminescence of the Largest Luminous Vertebrate, the Kitefin Shark, Dalatias licha: First Insights and Comparative Aspects
Authors: Mallefet Jérôme , Stevens Darren W. , Duchatelet Laurent
Published: February 2021

Bioluminescence has often been seen as a spectacular yet uncommon event at sea but considering the vastness of the deep sea and the occurrence of luminous organisms in this zone, it is now more and more obvious that producing light at depth must play an important role structuring the biggest ecosystem on our planet. Three species of deepwater sharks (Dalatias licha,Etmopterus lucifer, andEtmopterus granulosus) were collected from the Chatham Rise, off New Zealand, and for the first time, we documented their luminescence. Comparison of glowing shark pictures, combined with histological description of light organs and hormonal control analysis, highlight the evolutive conservation of the bioluminescence process within Dalatiidae and Etmopteridae. A special emphasis is placed on the luminescence ofD. licha, the largest known luminous vertebrate. This first experimental study of three luminous shark species from New Zealand provides an insight into the diversity of shark bioluminescence and highlights the need for more research to help understand these unusual deep-sea inhabitants: the glowing sharks.
Better for Whom? Leveling the Injustices of International Conferences by Moving Online
Authors: Niner Holly J. , Wassermann Sophia N.
Published: February 2021

International conferences are an important component of the professional calendar of scientists and practitioners in many fields, and are valued as opportunities to establish, create and foster networks, wellbeing and knowledge. The 2020 global pandemic, in prohibiting large gatherings and travel, has provided an opportunity to test the feasibility and implications of a shift from in-person to online conference formats. Avoiding international travel and associated bureaucracy, time and expense could overcome many of the historic injustices preventing many from participating in and benefiting from international conferences, and also avoid the emissions associated with international air travel. However, prior to 2020, there has been resistance to moving these events online because of the perception that the value of conferences cannot be cultivated online. Here, we use the example of the 6th International Marine Conservation Congress (IMCC6), which moved online in response to the COVID-19 pandemic, to explore participants’ perceptions and experiences of an online conference and the potential effects on access and inclusion. Our results show that moving online substantially increased the accessibility of the conference for those who would be unable to attend an in-person event for financial or personal reasons. Results also indicate that the online experience was able to recreate some of the benefits of in-person events, and that many participants are interested in attending online or virtual events in the future. However, the degree of enjoyment experienced or perceived ‘value’ likely relates to the frame of reference of the individual participant and a commitment to actively engage in the program. Reflecting on the success of IMCC6, we conclude that holding international conferences online, or at least including an online element as part of a ‘hybrid’ model, is a significant improvement in the capacity of conferences to meet the moral imperatives of the conservation community by addressing the climate crisis and some of the systemic injustices within the field.
Cephalotoxins: A Hotspot for Marine Bioprospecting?
Authors: Gonçalves Cátia , Costa Pedro M.
Published: February 2021

Molluscs provided one of the pioneering approved pharmaceuticals from the seas: the painkiller ziconotide, developed from an ω-conotoxin isolated from cone snails. As marine biotechnologists are turning towards the immense range of novel bioproducts from marine invertebrates, little attention has been given to cephalotoxins, a group of obscure proteinaceous toxins produced by the salivary glands of coleoids, i.e., octopuses, squids and cuttlefishes. These toxins, for which there is empirical evidence for acting as immobilisers at least against crustaceans, are proteinaceous substances among the many that comprise the venomous mixtures secreted by these animals. Despite the ecological and economical importance of cephalopods, little is known about cephalotoxins, beginning with the actual span of taxa that secrete them. Indeed, cephalopods are long suspected for producing specific toxins as part of their predation and defence mechanisms, making them a promising group of marine animals for the bioprospecting of novel compounds. Despite scant or absent toxicological or otherwise experimental evidence for their bioreactivity, advances in “omics” methods have shed some light in the molecular structure of cephalotoxins. There are reports of cephalotoxins being complex glycoproteins that take part in a myriad of novel compounds being produced by the salivary glands. Still, there is no consensus of cephalotoxins being a conserved form of proteins. As Blue Biotechnology and marine bioprospecting for novel bioreactives are gaining momentum, the present review will provide the state-of-the-art on cephalotoxins, highlighting old and new research and existing gaps in the current knowledge.
Compare the Effect of Inhaled Corticosteroids and Systemic Corticosteroids on Sputum Microbiome of AECOPD
Authors: Ma Nan , Qi Yujing , Liang Xiaona , Bai Jing , Deng Jingmin , Li Meihua , He Zhiyi
Published: February 2021

Background: To observe the effects of inhaled corticosteroids (ICS) and systemic corticosteroids (SCS) on the sputum microbiology of patients with AECOPD.

Methods: The 16S rRNA sequencing results for sputum samples from 36 admitted AECOPD patients were analyzed using ICS or SCS on the basis of standard treatment; sputum samples were collected before and after treatment for 1 day, 7, and 14 days.

Results: After 7 days of SCS treatment, the bacterial abundance of Sorangium, Acidibacter, and Fretibacterium decreased at the genus level. After 14 days of SCS treatment, the bacterial abundance of Prevotella_2, Bergeyella, Corynebacterium_1, and Ruminococcaceae_UCG-014 was decreased at the genus level, and an increase in the bacterial abundance of the Clostridiales_vadinBB60_group was observed at the family level. The linear discriminant analysis effect size (LEfSe) algorithm showed that after treatment for 14 days, Sphingobacterium increased in the SCS group, and Corynebacterium_1 (genus level), Bacillales (order level), and Lactobacillales (order level) decreased in the ICS group. However, the abundance of the above bacteria in each group of samples was <1%, suggesting that the two treatments may have similar effects on bacterial abundance. Alpha diversity analysis results showed that there was no significant difference in the ACE index, Chao1 index, Shannon index, or Simpson index between the ICS group and the SCS group. Beta diversity analysis showed that there was little difference in bacterial diversity among each group. BugBase predicted that although bacteria containing mobile elements in the SCS group decreased significantly compared with those in patients using ICS after treatment for 14 days, these two treatments had similar effects on other phenotype categories assigned to the bacterial contents.

Conclusions: Our results show that ICS and SCS have remarkably similar effects on the sputum microbiome of AECOPD patients.
Diagnosis of Hereditary TTP Caused by Homozygosity for a Rare Complex ADAMTS13 Allele After Salmonella Infection in a 43-Year-Old Asylum Seeker
Authors: Wendt Ralph , Kalbitz Sven , Otto Felix , Falter Tanja , Beige Joachim , Rossmann Heidi , Lämmle Bernhard
Published: February 2021

A 43-year-old Armenian patient was diagnosed with salmonella infection and thrombotic microangiopathy (TMA). The clinical course was benign with resolution of all laboratory alterations after antibiotic treatment. Constantly deficient ADAMTS13 activity without ADAMTS13 inhibitors and evidence of homozygosity for a rare complex ADAMTS13 allele led to the diagnosis of congenital thrombotic thrombocytopenic purpura (cTTP). Half-life of ADAMTS13 after plasma infusion was calculated (27,6h) and double blinded plasma infusion as well as ergometric exercise with and without prior plasma infusion undertaken to investigate suspected smoldering TTP activity.
miRNAs Flowing Up and Down: The Concerto of Psoriasis
Authors: Xiuli Yang , Honglin Wang
Published: February 2021

Psoriasis is a chronic immune-mediated skin disease, whose hallmarks include keratinocyte hyperproliferation and CD4+ T cell subsets imbalance. Dysregulated microRNAs (miRNAs) identified in psoriasis have been shown to affect keratinocyte and T cell functions, with studies on the molecular mechanisms and intrinsic relationships of the miRNAs on the way. Here, we focus on the dysregulated miRNAs that contribute to the two hallmarks of psoriasis with the miRNA target genes confirmed. We review a network, in which, upregulated miR-31/miR-203/miR-155/miR-21 and downregulated miR-99a/miR-125b facilitate the excessive proliferation and abnormal differentiation of psoriatic keratinocytes; upregulated miR-210 and downregulated miR-138 work in concert to distort CD4+ T cell subsets balance in psoriasis. The miRNAs exert their functions through regulating key psoriasis-associated transcription factors including NF-κB and STAT3. Whether flowing up or down, these miRNAs collaborate to promote the development and maintenance of psoriasis.
Terrestrial Inputs Shape Coastal Bacterial and Archaeal Communities in a High Arctic Fjord (Isfjorden, Svalbard)
Authors: Delpech Lisa-Marie , Vonnahme Tobias R. , McGovern Maeve , Gradinger Rolf , Præbel Kim , Poste Amanda E.
Published: February 2021

The Arctic is experiencing dramatic changes including increases in precipitation, glacial melt, and permafrost thaw, resulting in increasing freshwater runoff to coastal waters. During the melt season, terrestrial runoff delivers carbon- and nutrient-rich freshwater to Arctic coastal waters, with unknown consequences for the microbial communities that play a key role in determining the cycling and fate of terrestrial matter at the land-ocean interface. To determine the impacts of runoff on coastal microbial (bacteria and archaea) communities, we investigated changes in pelagic microbial community structure between the early (June) and late (August) melt season in 2018 in the Isfjorden system (Svalbard). Amplicon sequences of the 16S rRNA gene were generated from water column, river and sediment samples collected in Isfjorden along fjord transects from shallow river estuaries and glacier fronts to the outer fjord. Community shifts were investigated in relation to environmental gradients, and compared to river and marine sediment microbial communities. We identified strong temporal and spatial reorganizations in the structure and composition of microbial communities during the summer months in relation to environmental conditions. Microbial diversity patterns highlighted a reorganization from rich communities in June toward more even and less rich communities in August. In June, waters enriched in dissolved organic carbon (DOC) provided a niche for copiotrophic taxa including Sulfitobacter and Octadecabacter. In August, lower DOC concentrations and Atlantic water inflow coincided with a shift toward more cosmopolitan taxa usually associated with summer stratified periods (e.g., SAR11 Clade Ia), and prevalent oligotrophic marine clades (OM60, SAR92). Higher riverine inputs of dissolved inorganic nutrients and suspended particulate matter also contributed to spatial reorganizations of communities in August. Sentinel taxa of this late summer fjord environment included taxa from the class Verrucomicrobiae (Roseibacillus, Luteolibacter), potentially indicative of a higher fraction of particle-attached bacteria. This study highlights the ecological relevance of terrestrial runoff for Arctic coastal microbial communities and how its impacts on biogeochemical conditions may make these communities susceptible to climate change.
A Multiyear Survey and Identification of Pepper- and Tomato-Infecting Viruses in Yunnan Province, China
Authors: Li Yueyue , Tan Guanlin , Xiao Long , Zhou Wenpeng , Lan Pingxiu , Chen Xiaojiao , Liu Yong , Li Ruhui , Li Fan
Published: February 2021

During pepper and tomato production seasons in 2013–2017, large-scale virus disease surveys were conducted in different regions of Yunnan Province, China. A total of 1,267 pepper and tomato samples with various virus-like symptoms were collected and analyzed for virus infections through dot enzyme-linked immunosorbent assay (dot-ELISA), polymerase chain reaction (PCR), and reverse-transcription (RT)-PCR. The detection results showed that 19 different viruses were present in about 50.9% of the assayed samples, and among these viruses, seven viruses were found in both pepper and tomato samples. Mixed infections with two to three of the 15 identified mixed infection types were found in the pepper samples and 10 identified mixed infection types were found in the tomato samples. Among the infected samples, Tomato spotted wilt orthotospovirus (TSWV) was the most common virus, with a detection rate of about 20.0% followed by Pepper vein yellows virus (PeVYV, 13.0%). This survey revealed for the first time that pepper is a natural host of Tobacco vein distorting virus (TVDV) worldwide and tomato is a natural host of Potato leafroll virus (PLRV) in China. PeVYV, Tobacco mild green mosaic virus (TMGMV) and Wild tomato mosaic virus (WTMV) were first time found in pepper and Tomato mottle mosaic virus (ToMMV) and Chilli veinal mottle virus (ChiVMV) were first time found in tomato in Yunnan Province. Finally, the virus incidences were higher in Kunming, Yuxi, Chuxiong, and Honghe region than other regions.
Seed Biopriming With Trichoderma Strains Isolated From Tree Bark Improves Plant Growth, Antioxidative Defense System in Rice and Enhance Straw Degradation Capacity
Authors: Swain Harekrushna , Adak Totan , Mukherjee Arup K. , Sarangi Sarmistha , Samal Pankajini , Khandual Ansuman , Jena Rupalin , Bhattacharyya Pratap , Naik Soumendra K. , Mehetre Sayaji T. , Baite Mathew S. , Kumar M Sunil , Zaidi Najam Waris
Published: February 2021

This study is a unique report of the utilization of Trichoderma strains collected from even tree barks for rice plant growth, its health management, and paddy straw degradation. Seven different spp. of Trichoderma were characterized according to morphological and molecular tools. Two of the isolated strains, namely Trichoderma hebeiensis and Trichoderma erinaceum, outperformed the other strains. Both of the strains controlled four important rice pathogens, i.e., Rhizoctonia solani (100%), Sclerotium oryzae (84.17%), Sclerotium rolfsii (66.67%), and Sclerotium delphinii (76.25%). Seed bio-priming with respective Trichoderma strains reduced the mean germination time, enhanced the seedling vigor and total chlorophyll content which could be related to the higher yield observed in two rice varieties; Annapurna and Satabdi. All the seven strains accelerated the decomposition of rice straw by producing higher straw degrading enzymes like total cellulase (0.97–2.59 IU/mL), endoglucanase (0.53–0.75 IU/mL), xylanase (145.35–201.35 nkat/mL), and laccase (2.48–12.60 IU/mL). They also produced higher quantities of indole acetic acid (19.19–46.28 μg/mL), soluble phosphate (297.49–435.42 μg/mL), and prussic acid (0.01–0.37 μg/mL) which are responsible for plant growth promotion and the inhibition of rice pathogen populations. Higher expression of defense enzymes like catalase (≥250% both in shoot and root), peroxidase (≥150% in root and ≥100% in shoot), superoxide dismutase (≥ 150% in root and ≥100% in shoot), polyphenol oxidase (≥160% in shoot and ≥120% in shoot), and total phenolics (≥200% in root and ≥250% in shoot) as compared to the control indicates stress tolerance ability to rice crop. The expression of the aforementioned enzymes were confirmed by the expression of corresponding defense genes like PAL (>3-fold), DEFENSIN (>1-fold), POX (>1.5-fold), LOX (>1-fold), and PR-3 (>2-fold) as compared to the non-treated control plants. This investigation demonstrates that Trichoderma strains obtained from tree bark could be considered to be utilized for the sustainable health management of rice crop.
Effect of Low-Input Organic and Conventional Farming Systems on Maize Rhizosphere in Two Portuguese Open-Pollinated Varieties (OPV), “Pigarro” (Improved Landrace) and “SinPre” (a Composite Cross Population)
Authors: Ares Aitana , Costa Joana , Joaquim Carolina , Pintado Duarte , Santos Daniela , Messmer Monika M. , Mendes-Moreira Pedro M.
Published: February 2021

Maize is one of the most important crops worldwide and is the number one arable crop in Portugal. A transition from the conventional farming system to organic agriculture requires optimization of cultivars and management, the interaction of plant–soil rhizosphere microbiota being pivotal. The objectives of this study were to unravel the effect of population genotype and farming system on microbial communities in the rhizosphere of maize. Rhizosphere soil samples of two open-pollinated maize populations (“SinPre” and “Pigarro”) cultivated under conventional and organic farming systems were taken during flowering and analyzed by next-generation sequencing (NGS). Phenological data were collected from the replicated field trial. A total of 266 fungi and 317 bacteria genera were identified in “SinPre” and “Pigarro” populations, of which 186 (69.9%) and 277 (87.4%) were shared among them. The microbiota of “Pigarro” showed a significant higher (P < 0.05) average abundance than the microbiota of “SinPre.” The farming system had a statistically significant impact (P < 0.05) on the soil rhizosphere microbiota, and several fungal and bacterial taxa were found to be farming system-specific. The rhizosphere microbiota diversity in the organic farming system was higher than that in the conventional system for both varieties. The presence of arbuscular mycorrhizae (Glomeromycota) was mainly detected in the microbiota of the “SinPre” population under the organic farming systems and very rare under conventional systems. A detailed metagenome function prediction was performed. At the fungal level, pathotroph–saprotroph and pathotroph–symbiotroph lifestyles were modified by the farming system. For bacterial microbiota, the main functions altered by the farming system were membrane transport, transcription, translation, cell motility, and signal transduction. This study allowed identifying groups of microorganisms known for their role as plant growth-promoting rhizobacteria (PGPR) and with the capacity to improve crop tolerance for stress conditions, allowing to minimize the use of synthetic fertilizers and pesticides. Arbuscular mycorrhizae (phyla Glomeromycota) were among the most important functional groups in the fungal microbiota and Achromobacter, Burkholderia, Erwinia, Lysinibacillus, Paenibacillus, Pseudomonas, and Stenotrophomonas in the bacterial microbiota. In this perspective, the potential role of these microorganisms will be explored in future research.
Systematic and Multi-Omics Prognostic Analysis of Lysine Acetylation Regulators in Glioma
Authors: Tu Zewei , Wu Lei , Luo Haitao , Li Jingying , Lv Shigang , Ye Minhua , Liu Feng , Tao Chuming , Zhu Xingen , Huang Kai
Published: February 2021

Lysine acetylation modification, which has key roles in cellular homeostasis as well as cancer malignancy, is dynamically regulated by lysine acetylation regulators (LARs). In our study, we found that most of 33 evaluated LARs were differentially expressed among 1,125 gliomas grouped by different clinicopathological characteristics. Consensus clustering was applied to 33 LARs, resulting in three glioma subtypes (LA1, 2, and 3). The LA3 subgroup was associated with the poorest clinical outcome, higher WHO grade, fewer isocitrate dehydrogenase mutations, and lower frequency of 1p/19q codeletion. Furthermore, gene set enrichment analysis indicated that eight tumor hallmarks were highly enriched in the LA3 subgroup. These results suggested that LARs are significantly related to glioma malignancy. We then designed a LAR-signature based on 14 overall survival (overall survival)-related LARs, and showed that the LAR-signature possesses strong and independent prognostic value for glioma patients in both training and validation datasets. Moreover, by interrogating single nucleotide polymorphism and copy number variation (CNV) data in The Cancer Genome Atlas dataset, we found that higher score of our risk signature is correlated with the hypermutation status of gliomas and that HDAC1(1p) was one of the oncogenes lost in 1p/19q codeletion events, while SIRT2(19q) and EP300(22q) may act as tumor suppressors in gliomas with 19q or 22q deletions, respectively. In conclusion, LARs are critical for the malignant development of gliomas, and our results are useful for prognostic stratification and development of novel assessment strategies for the prognosis of glioma patients.
The Association of Suppressed Hypoxia-Inducible Factor-1 Transactivation of Angiogenesis With Defective Recovery From Cerebral Ischemic Injury in Aged Rats
Authors: Guo Yingjia , Zhou Junpeng , Li Xianglong , Xiao Ying , Zhang Jingyao , Yang Yutao , Feng Li , Kang Y. James
Published: February 2021

Elderly patients suffer more brain damage in comparison with young patients from the same ischemic stroke. The present study was undertaken to test the hypothesis that suppressed hypoxia-inducible factor-1 (HIF-1) transcription activity is responsible for defective recovery after ischemic stroke in the elders. Aged and young rats underwent 1-h transient middle cerebral artery occlusion (MCAO) to produce cerebral ischemic injury. The initial cerebral infarct volume in the young gradually declined as time elapsed, but in the aged rats remained the same. The defective recovery in the aged was associated with depressed angiogenesis and retarded neurorestoration. There was no difference in HIF-1α accumulation in the brain between the two age groups, but the expression of HIF-1 regulated genes involved in cerebral recovery was suppressed in the aged. In confirmation, inhibition of HIF-1 transactivation of gene expression in the young suppressed cerebral recovery from MCAO as the same as that observed in the aged rats. Furthermore, a copper metabolism MURR domain 1 (COMMD1) was significantly elevated after MCAO only in the brain of aged rats, and suppression of COMMD1 by siRNA targeting COMMD1 restored HIF-1 transactivation and improved recovery from MCAO-induced damage in the aged brain. These results demonstrate that impaired HIF-1 transcription activity, due at least partially to overexpression of COMMD1, is associated with the defective cerebral recovery from ischemic stroke in the aged rats.