Summary
Unlike immunoglobulin (Ig)G pneumococcal polysaccharide (PnPS)‐antibodies, PnPS IgA and IgM‐antibodies are not routinely determined for the assessment of immunocompetence. It is not yet known ...whether an isolated inability to mount a normal IgM or IgA‐PnPS response should be considered a relevant primary antibody deficiency (PAD). We studied the clinical relevance of anti‐PnPS IgM and IgA‐assays in patients with suspected primary immunodeficiency in a large teaching hospital in ’s‐Hertogenbosch, the Netherlands. Serotype‐specific‐PnPS IgG assays were performed; subsequently, 23‐valent‐PnPS IgG assays (anti‐PnPS IgG assays), and later anti‐PnPS IgA and IgM assays, were performed in archived material (240 patients; 304 samples). Eleven of 65 pre‐ and six of 10 post‐immunization samples from good responders to PnPS serotype‐specific IgG testing had decreased anti‐PnPS IgA and/or IgM titres. Of these, three pre‐ and no post‐immunization samples were from patients previously classified as ‘no PAD’. Determination of anti‐PnPS IgA and IgM in addition to anti‐PnPS IgG did not reduce the need for serotype‐specific PnPS IgG testing to assess immunocompetence receiver operating characteristic (ROC) analysis of post‐immunization samples: anti‐PnPS IgA + IgG area under the curve (AUC) = 0.80, 95% confidence interval (CI) = 0.63–0.97; anti‐PnPS IgM + IgG AUC 0.80, 95% CI = 0.62–0.98; anti‐PnPS IgA + IgG + IgM AUC = 0.71, 95% CI = 0.51–0.91; anti‐PnPS IgG AUC = 0.93, 95% CI = 0.85–1.00. Our data show that patients classified as having an intact antibody response based on measurement of serotype‐specific PnPS IgG can still display impaired anti‐PnPS IgM and IgA responses, and that the additional measurement of anti‐PnPS IgA and IgM could not reduce the need for serotype‐specific IgG testing. Future studies are needed to investigate the clinical relevance of potential ‘specific IgA or IgM antibody deficiency’ in patients with recurrent airway infections in whom no PAD could be diagnosed according to the current definitions.
Patients classified as having an intact PnPS IgG antibody response, still can display defective anti‐PnPS IgA and IgM responses. Whether ‘specific IgA or IgM antibody deficiency’ is a clinically relevant form of antibody deficiency should be investigated in future studies.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of ...biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.
In this study, one water soluble polysaccharide (IOP1–1) with a weight average molecular weight of 6886 Da was obtained from the black crystal region of Inonotus obliquus by hot water extraction, ...DEAE-52 cellulose extraction and Sephadex-100 column chromatography purification. Structural analysis indicated that IOP1–1 was a glucan with a main chain composed of α-Glcp-(1 → 4)-α-Glcp-(1 → 4)-β-Glcp-(1 → 4)-β-Glcp-(1 → 4)-α-Glcp-(1 → 6)-β-Glcp-(1 → 4)-α-Glcp-(1 → 3)-β-Glcp-(1→. The CCK-8 assay results showed that IOP1–1 inhibited AsPC-1 and SW1990 pancreatic cancer cell proliferation in a concentration-dependent manner. Flow cytometric analysis revealed that IOP1–1 induced cell cycle arrest in AsPC-1 and SW1990 cells. Hoechst 33342 staining and Annexin V-FITC/PI double staining analysis showed that IOP1–1 could induce apoptosis in AsPC-1 and SW1990 cells. Furthermore, western blot analysis confirmed that IOP1–1 could induce apoptosis in AsPC-1 and SW1990 pancreatic cancer cells through three pathways: the mitochondrial pathway, the death receptor pathway, and endoplasmic reticulum stress. According to these research data, IOP1–1 may be utilized as an adjuvant treatment to anticancer medications, opening up new application prospects and opportunities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bacterial pathogens and commensals are surrounded by diverse surface polysaccharides which include capsules and lipopolysaccharides. These carbohydrates play a vital role in bacterial ecology and ...interactions with the environment. Here, we review recent rapid advancements in this field, which have improved our understanding of the roles, structures, and genetics of bacterial polysaccharide antigens. Genetic loci encoding the biosynthesis of these antigens may have evolved as bacterial diversity-generating machines, driven by selection from a variety of forces, including host immunity, bacteriophages, and cell–cell interactions. We argue that the high adaptive potential of polysaccharide antigens should be taken into account in the design of polysaccharide-targeting medical interventions like conjugate vaccines and phage-based therapies.
Recent advances in glycobiology emphasise the importance of surface carbohydrates in the evolution of bacterial commensals and pathogens.
Epidemiological and genomic analyses highlight the remarkable diversity and adaptability of bacterial surface polysaccharides, often driven by horizontal DNA transfer.
Functional heterogeneity of bacterial polysaccharide antigens points to multiple factors which have shaped their diversity.
Antigenic diversity is a challenge for polysaccharide conjugate vaccines which strive to eliminate some bacterial diseases, like the pneumococcal disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The evolution and genomic basis of beetle diversity McKenna, Duane D.; Shin, Seunggwan; Ahrens, Dirk ...
Proceedings of the National Academy of Sciences - PNAS,
12/2019, Volume:
116, Issue:
49
Journal Article
Peer reviewed
Open access
The order Coleoptera (beetles) is arguably the most speciose group of animals, but the evolutionary history of beetles, including the impacts of plant feeding (herbivory) on beetle diversification, ...remain poorly understood. We inferred the phylogeny of beetles using 4,818 genes for 146 species, estimated timing and rates of beetle diversification using 89 genes for 521 species representing all major lineages and traced the evolution of beetle genes enabling symbiont-independent digestion of lignocellulose using 154 genomes or transcriptomes. Phylogenomic analyses of these uniquely comprehensive datasets resolved previously controversial beetle relationships, dated the origin of Coleoptera to the Carboniferous, and supported the codiversification of beetles and angiosperms. Moreover, plant cell wall-degrading enzymes (PCWDEs) obtained from bacteria and fungi via horizontal gene transfers may have been key to the Mesozoic diversification of herbivorous beetles—remarkably, both major independent origins of specialized herbivory in beetles coincide with the first appearances of an arsenal of PCWDEs encoded in their genomes. Furthermore, corresponding (Jurassic) diversification rate increases suggest that these novel genes triggered adaptive radiations that resulted in nearly half of all living beetle species. We propose that PCWDEs enabled efficient digestion of plant tissues, including lignocellulose in cell walls, facilitating the evolution of uniquely specialized plant-feeding habits, such as leaf mining and stem and wood boring. Beetle diversity thus appears to have resulted from multiple factors, including low extinction rates over a long evolutionary history, codiversification with angiosperms, and adaptive radiations of specialized herbivorous beetles following convergent horizontal transfers of microbial genes encoding PCWDEs.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
•The ulvan extracted from Ulva clathrata was degraded by a specific ulvan lyase.•The detailed structure of the degraded oligosaccharides was resolved by MS and NMR.•This ulvan mainly consists of ...→4)-β-d-GlcA-(1→4)-α-l-Rha3S-(1→ repeating units.•There is a long side branch in the ulvan structure.
Rhamnan-rich sulfated polysaccharides extracted from green algae (ulvan) constitute potentially useful natural materials for drug development. However, the characterization of their complex structures poses a challenge for their application. In this study, the structure of ulvan extracted from Ulva clathrata was analyzed with the assistance of an ulvan lyase belonging to the PL25 family. According to mass spectrometry and nuclear magnetic resonance analysis of the degraded oligosaccharides, the backbone of such a polysaccharide mainly consisted of →4)-β-d-GlcA-(1→4)-α-l-Rha3S-(1→ and →4)-β-d-Xyl-(1→4)-α-l-Rha3S-(1→ disaccharide repeating units, and the ratio is approximately 4:1. In addition, about 4% of the xylose moieties bear sulfate groups. Minor amounts of branches containing hexose and unsaturated glucuronic acid were found during the sequence analysis of hexa- to octasaccharides. These results indicated the presence of a long branch in the ulvan. The clarification of the detailed structure provides a foundation for ulvan modification and its structure-activity relationship studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Euganean Thermal District, situated in North-East Italy, is one of Europe's largest and oldest thermal centres. The topical application of its therapeutic thermal muds is recognised by the ...Italian Health System as a beneficial treatment for patients suffering from arthro-rheumatic diseases. Polysaccharides produced by the mud microbiota have been recently identified as anti-inflammatory bioactive molecules. In this paper we analysed the efficacy of Microbial-Polysaccharides (M-PS) derived from mature muds obtained at different maturation temperatures, both within and outside the codified traditional mud maturation range. M-PSs were extracted from six mature muds produced by five spas of the Euganean Thermal District and investigated for their chemical properties, monosaccharide composition and in vivo anti-inflammatory potential, using the zebrafish model organism. Additionally, mature muds were characterized for their microbiota composition using Next-Generation Sequencing. The results showed that all M-PSs exhibit similar anti-inflammatory potential, referable to their comparable chemical composition. This consistency was observed despite changes in cyanobacteria populations, suggesting a possible role of the entire microbial community in shaping the properties of these biomolecules. These findings highlight the importance of scientific research in untangling the origins of the therapeutic efficacy of Euganean Thermal muds in the treatment of chronic inflammatory conditions.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Macroalgae species are fast growing and their polysaccharides are already used as food ingredient due to their properties as hydrocolloids or they have potential high value bioactivity. The ...degradation of these valuable polysaccharides to access the sugar components has remained mostly unexplored so far. One reason is the high structural complexity of algal polysaccharides, but also the need for suitable enzyme cocktails to obtain oligo‐ and monosaccharides. Among them, there are several rare sugars with high value. Recently, considerable progress was made in the discovery of highly specific carbohydrate‐active enzymes able to decompose complex marine carbohydrates such as carrageenan, laminarin, agar, porphyran and ulvan. This minireview summarizes these achievements and highlights potential applications of the now accessible abundant renewable resource of marine polysaccharides.
Algae biomass is a source for many valuable compounds for the pharmaceutical and chemical industry. Especially marine polysaccharides contain rare sugars of interest, but a major bottleneck is access to these sugars. In this mini‐review the common knowledge of marine CAZyme‐based deconstruction of these polysaccharides and the biotechnological potential of the thus accessible oligo‐ and monosugars are described.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Ulvan is a major cell wall component of green algae of the genus Ulva, and some marine bacteria encode enzymes that can degrade this polysaccharide. The first ulvan-degrading lyases have been ...recently characterized, and several putative ulvan lyases have been recombinantly expressed, confirmed as ulvan lyases, and partially characterized. Two families of ulvan-degrading lyases, PL24 and PL25, have recently been established. The PL24 lyase LOR_107 from the bacterial Alteromonadales sp. strain LOR degrades ulvan endolytically, cleaving the bond at the C4 of a glucuronic acid. However, the mechanism and LOR_107 structural features involved are unknown. We present here the crystal structure of LOR_107, representing the first PL24 family structure. We found that LOR_107 adopts a seven-bladed β-propeller fold with a deep canyon on one side of the protein. Comparative sequence analysis revealed a cluster of conserved residues within this canyon, and site-directed mutagenesis disclosed several residues essential for catalysis. We also found that LOR_107 uses the His/Tyr catalytic mechanism, common to several PL families. We captured a tetrasaccharide substrate in the structures of two inactive mutants, which indicated a two-step binding event, with the first substrate interaction near the top of the canyon coordinated by Arg320, followed by sliding of the substrate into the canyon toward the active-site residues. Surprisingly, the LOR_107 structure was very similar to that of the PL25 family PLSV_3936, despite only ∼14% sequence identity between the two enzymes. On the basis of our structural and mutational analyses, we propose a catalytic mechanism for LOR_107 that differs from the typical His/Tyr mechanism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Marine green algae are valuable sources of diverse health-promoting bioactive components. Ulvan is suitable for biological applications due to its unique structure and numerous bioactivities. Here, ...the complex structure of ulvan from Ulva pertusa was analyzed using specific ulvan lyase degradation, MS, and NMR detection. Its structure mainly consists of →4)-β-d-GlcA-(1 → 4)-α-l-Rha3S-(1 → and →4)-β-d-Xyl-(1 → 4)-α-l-Rha3S-(1 → repeating units. Small amounts of →4)-α-l-IdoA-(1 → 4)-α-l-Rha3S-(1 → unit also exist. In addition, a minor number of branches, a single GlcA, and a long branch containing GlcA-Glc were linked to Rha3S. The antiviral activity of the ulvan and its degraded fragments were further investigated. Ulvan (1068.2 kDa) and ulvan-F1 (38.5 kDa) with relatively high molecular weight showed potency of inhibiting the infection and replication of vesicular stomatitis virus (VSV) at 100 μg/mL, the inhibition rate of VSV replication was 40.75% and 40.13%, respectively. These results indicated that ulvan has potential as a functional agent.
•An ulvan lyase was used for the structure analysis of ulvan-F0 from Ulva pertusa.•Ulvan-F0 consists of three repeating disaccharide units and two side branches.•Molecular weight significantly affects the antiviral activity of ulvan.•Ulvan-F0 and ulvan-F1 (38.5 kDa) could inhibit the infection and replication of VSV.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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