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The General Budget of the Nation (PNG) is the instrument for the allocation of financial resources for the fulfillment of state policies and objectives; it contemplates the amount, the origin of the income, the amount of the authorized expenses and the financing mechanisms. Similarly, the PNG as a system is constituted by a set of standards, techniques, methods and procedures used that involves various agencies during the phases of programming, formulation, approval, execution, modification, control and evaluation of financial resources (Congress National of the Republic of Paraguay, 2021).

Peptidoglycan recognition proteins (PGRPs) are a family of pattern recognition receptors (PRRs) involved in host antibacterial responses, and their functions have been characterized in most invertebrate and vertebrate animals. However, little information is available regarding the potential function of PGRPs in the giant triton snail Charonia tritonis. In this study, a short-type PGRP gene (termed Ct-PGRP-S1) was identified in C. tritonis. Ct-PGRP-S1 was predicted to contain several structural features known in PGRPs, including a typical PGRP domain (Amidase_2) and Src homology-3 (SH3) domain. The Ct-PGRP-S1 gene was constitutively expressed in all tissues examined except in proboscis, with the highest expression level observed in the liver. As a typical PRR, Ct-PGRP-S1 has an ability to degrade peptidoglycan (PGN) and was proven to have non-Zn2+-dependent amidase activity and antibacterial activity against Vibrioalginolyticus and Staphylococcus aureus. It is the first report to reveal the peptidoglycan recognition protein in C. tritonis, and these results suggest that peptidoglycan recognition protein Ct-PGRP-S1 is an important effector of C. tritonis that modulates bacterial infection resistance of V. alginolyticus and S. aureus, and this study may provide crucial basic data for the understanding of an innate immunity system of C. tritonis. [ABSTRACT FROM AUTHOR]

Peptidoglycan recognition proteins (PGRPs) are a family of pattern recognition receptors (PRRs) involved in host antibacterial responses, and their functions have been characterized in most invertebrate and vertebrate animals. However, little information is available regarding the potential function of PGRPs in the giant triton snail Charonia tritonis. In this study, a short-type PGRP gene (termed Ct-PGRP-S1) was identified in C. tritonis. Ct-PGRP-S1 was predicted to contain several structural features known in PGRPs, including a typical PGRP domain (Amidase_2) and Src homology-3 (SH3) domain. The Ct-PGRP-S1 gene was constitutively expressed in all tissues examined except in proboscis, with the highest expression level observed in the liver. As a typical PRR, Ct-PGRP-S1 has an ability to degrade peptidoglycan (PGN) and was proven to have non-Zn2+-dependent amidase activity and antibacterial activity against Vibrioalginolyticus and Staphylococcus aureus. It is the first report to reveal the peptidoglycan recognition protein in C. tritonis, and these results suggest that peptidoglycan recognition protein Ct-PGRP-S1 is an important effector of C. tritonis that modulates bacterial infection resistance of V. alginolyticus and S. aureus, and this study may provide crucial basic data for the understanding of an innate immunity system of C. tritonis.

The apextrin C-terminal (ApeC) domain is a class of newly discovered protein domains with an origin dating back to prokaryotes. ApeC-containing proteins (ACPs) have been found in various marine and aquatic invertebrates, but their functions and the underlying mechanisms are largely unknown. Early studies suggested that amphioxus ACP1 and ACP2 bind to bacterial cell walls and have a role in immunity. Here we identified another two amphioxus ACPs (ACP3 and ACP5), which belong to the same phylogenetic clade with ACP1/2, but show distinct expression patterns and sequence divergence (40-50% sequence identities). Both ACP3 and ACP5 were mainly expressed in the intestine and hepatic cecum, and could be up-regulated after bacterial challenge. Both prokaryotic-expressed recombinant ACP3 and ACP5 could bind with several species of bacteria and yeasts, showing agglutinating activity but no microbicidal activity. ELISA assays suggested that their ApeC domains could interact with peptidoglycan (PGN), but not with lipoteichoic acid (LTA), lipopolysaccharides (LPS) and zymosan A. Furthermore, they can only bind to Lys-type PGN from Staphylococcus aureus, but not to DAP-type PGN from Bacillus subtilis and not to moieties of PGN such as MDPs, NAMs and NAGs. This recognition spectrum is different from that of ACP1/2. We also found that when expressed in mammalian cells, ACP3 could interact with TRAF6 via a conserved non-ApeC region, which inhibited the ubiquitination of TRAF6 and hence suppressed downstream NF-κB activation. This work helped define a novel subfamily of ACPs, which have conserved structures, and have related yet diversified molecular functions. Its members have dual roles, with ApeC as a lectin and a conserved unknown region as a signal transduction regulator. These findings expand our understanding of the ACP functions and may guide future research on the role of ACPs in different animal clades.

The apextrin C-terminal (ApeC) domain is a class of newly discovered protein domains with an origin dating back to prokaryotes. ApeC-containing proteins (ACPs) have been found in various marine and aquatic invertebrates, but their functions and the underlying mechanisms are largely unknown. Early studies suggested that amphioxus ACP1 and ACP2 bind to bacterial cell walls and have a role in immunity. Here we identified another two amphioxus ACPs (ACP3 and ACP5), which belong to the same phylogenetic clade with ACP1/2, but show distinct expression patterns and sequence divergence (40-50% sequence identities). Both ACP3 and ACP5 were mainly expressed in the intestine and hepatic cecum, and could be up-regulated after bacterial challenge. Both prokaryotic-expressed recombinant ACP3 and ACP5 could bind with several species of bacteria and yeasts, showing agglutinating activity but no microbicidal activity. ELISA assays suggested that their ApeC domains could interact with peptidoglycan (PGN), but not with lipoteichoic acid (LTA), lipopolysaccharides (LPS) and zymosan A. Furthermore, they can only bind to Lys-type PGN from Staphylococcus aureus , but not to DAP-type PGN from Bacillus subtilis and not to moieties of PGN such as MDPs, NAMs and NAGs. This recognition spectrum is different from that of ACP1/2. We also found that when expressed in mammalian cells, ACP3 could interact with TRAF6 via a conserved non-ApeC region, which inhibited the ubiquitination of TRAF6 and hence suppressed downstream NF-κB activation. This work helped define a novel subfamily of ACPs, which have conserved structures, and have related yet diversified molecular functions. Its members have dual roles, with ApeC as a lectin and a conserved unknown region as a signal transduction regulator. These findings expand our understanding of the ACP functions and may guide future research on the role of ACPs in different animal clades. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction critically contributes to many major human diseases. The impact of specific gut microbial metabolites on mitochondrial functions of animals and the underlying mechanisms remain to be uncovered. Here, we report a profound role of bacterial peptidoglycan muropeptides in promoting mitochondrial functions in multiple mammalian models. Muropeptide addition to human intestinal epithelial cells (IECs) leads to increased oxidative respiration and ATP production and decreased oxidative stress. Strikingly, muropeptide treatment recovers mitochondrial structure and functions and inhibits several pathological phenotypes of fibroblast cells derived from patients with mitochondrial disease. In mice, muropeptides accumulate in mitochondria of IECs and promote small intestinal homeostasis and nutrient absorption by modulating energy metabolism. Muropeptides directly bind to ATP synthase, stabilize the complex, and promote its enzymatic activity in vitro, supporting the hypothesis that muropeptides promote mitochondria homeostasis at least in part by acting as ATP synthase agonists. This study reveals a potential treatment for human mitochondrial diseases., Competing Interests: Declaration of interests The University of Colorado has filed a US patent application, "Novel therapeutic methods of using pertidoglycan muropeptides to promote ATP synthase activity and mitochondrial homeostasis and development" (application no. PCT/US22/74654, filed August 8, 2022), partly based on results from this study (WO2023019100A2)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pharyngitis is an inflammation of the pharynx caused by viral, bacterial, or non-infectious factors. In the present study, the anti-inflammatory efficacy of carvacrol was assessed using an in vitro model of streptococcal pharyngitis using human tonsil epithelial cells (HTonEpiCs) induced with Streptococcus pyogenes cell wall antigens. HTonEpiCs were stimulated by a mixture of lipoteichoic acid (LTA) and peptidoglycan (PGN) for 4 h followed by exposure to carvacrol for 20 h. Following exposure, interleukin (IL)-6, IL-8, human beta defensin-2 (HBD-2), epithelial-derived neutrophil-activating protein-78 (ENA-78), granulocyte chemotactic protein-2 (GCP-2), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and prostaglandin (PGE2) were measured by enzyme-linked immunosorbent assays (ELISA). The levels of pro-inflammatory cytokines, IL-6, IL-8, ENA-78, and GCP-2 were decreased in a carvacrol dose-dependent manner. The production of HBD-2 was significantly suppressed over 24 h carvacrol treatments. PGE2 and COX-2 levels in the cell suspensions were affected by carvacrol treatment. TNF-α was not detected. The cell viability of all the tested carvacrol concentrations was greater than 80%, with no morphological changes. The results suggest that carvacrol has anti-inflammatory properties, and carvacrol needs to be further assessed for potential clinical or healthcare applications to manage the pain associated with streptococcal pharyngitis.

Salivary peroxidase and myeloperoxidase are known to display antibacterial activity against oral microbes, and previous indications have pointed to the possibility that horseradish peroxidase (HRP) adsorbs onto the membrane of the major oral streptococci, Streptococcus mutans and Streptococcus sanguinis (S. sanguinis). However, the mechanism of interaction between HRP and the bacterial cell wall component is unclear. Dental plaques containing salivary glycoproteins and extracellular microbial products are visualized with 'dental plaque disclosing agent', and are controlled within dental therapy. However, current 'dental plaque disclosing agents' are difficult to evaluate with just dental plaques, since they stain and disclose not only dental plaques but also pellicle formed with salivary glycoproteins on a tooth surface. In this present study, we have demonstrated that HRP interacted with the cell wall component of the major gram-positive bacterial peptidoglycan, but not the major cell wall component of gram-negative bacteria lipopolysaccharide. Furthermore, we observed that the adsorbed HRP labeled with fluorescence was detected on the major oral gram-positive strains S. sanguinis and Streptococcus salivarius (S. salivarius), but not on a gram-negative strain, Escherichia coli (E. coli). Furthermore, we have demonstrated that the combination of HRP and chromogenic substrate clearly disclosed the dental plaques and the biofilm developed by S. sanguinis, S. salivarius and the major gram-postive bacteria Lactobacillus casei on tooth surfaces, and slightly disclosed the biofilm by E. coli. The combination of HRP and chromogenic substrate did not stain either the dental pellicle with the salivary glycoprotein mucin, or naked tooth surfaces. These results have suggested the possibility that the adsorption activity of HRP not only contributes to the evaluation of dental plaque, but that enzymatic activity of HRP may also contribute to improve dental hygiene. [ABSTRACT FROM AUTHOR]

Numerous studies have shown that microbiomes play an important role in the pathogenesis of chronic rhinosinusitis (CRS). In addition to a known short pentraxin, C-reactive protein, long pentraxin 3 (PTX3) belongs to pentraxin family which detects conserved microbial pentraxin motifs and mobilizes early defense against foreign invaders, but its participation in CRS remains unclear. In the present study, through an intensive screening, peptidoglycan (PGN) was selected as a main material to investigate the action mechanism of a cell wall component on CRS without nasal polyps (CRSsNP) nasal mucosa-derived fibroblasts and the PTX3 expression in human nasal mucosa tissue and discharge. The PGN not only enhanced PTX3 mRNA and protein production in cells but also caused marked PTX3 secretion into extracellular space. The pharmacological interventions indicated that the PTX3 induction was mediated mainly through toll-like receptor 2 (TLR2), phosphoinositide-phospholipase C (PI-PLC), protein kinase C (PKC), NF-κB, and cAMP response element binding protein (CREB), which was further confirmed by the observations that a direct PKC activator (phorbol ester) had a similar inductory effect on PTX3 expression/production and the siRNA interference knockdown of PKCμ/δ, NF-κB, and CREB compromised PTX3 production. Meanwhile, PTX3 was found to be overexpressed/produced in nasal mucosa and discharge/secretion of the CRSsNP patients. Collectively, we first demonstrated here that PGN enhances PTX3 expression and release in nasal fibroblasts through TLR2, PI-PLC, PKCμ/δ, NF-κB, and CREB signaling pathways. The PTX3 is overexpressed in nasal mucosa and discharge/secretion of CRSsNP patients, revealing its possible importance in CRSsNP development and progression. Key messages: Long pentraxin 3 (PTX3) is highly expressed in nasal mucosa and discharge/secretion of patients of chronic rhinosinusitis without nasal polyps (CRSsNP). The bacteria cell wall component-peptidoglycan (PGN) causes PTX3 expression in CRSsNP nasal mucosa-derived fibroblasts, contributing to the PTX3 increase in tissues. PGN induces PTX3 expression through a previously known IκB/NF-κB and a novel PKCμ/δ and CREB signaling pathway. The PTX3 may be used as a biomarker for CRS. [ABSTRACT FROM AUTHOR]

Background: Transcriptomic responses to immune stimulation were investigated in coho salmon (Oncorhynchus kisutch) with distinct growth phenotypes. Wild-type fish were contrasted to strains with accelerated growth arising either from selective breeding (i.e. domestication) or genetic modification. Such distinct routes to accelerated growth may have unique implications for relationships and/or trade-offs between growth and immune function. Results: RNA-Seq was performed on liver and head kidney in four 'growth response groups' injected with polyinosinic-polycytidylic acid (Poly I:C; viral mimic), peptidoglycan (PGN; bacterial mimic) or PBS (control). These groups were: 1) 'W': wild-type, 2) 'TF': growth hormone (GH) transgenic salmon with ~ 3-fold higher growth-rate than W, 3) 'TR': GH transgenic fish ration restricted to possess a growth-rate equal to W, and 4) 'D': domesticated non-transgenic fish showing growth-rate intermediate to W and TF. D and TF showed a higher similarity in transcriptomic response compared to W and TR. Several immune genes showed constitutive expression differences among growth response groups, including perforin 1 and C-C motif chemokine 19-like. Among the affected immune pathways, most were up-regulated by Poly I:C and PGN. In response to PGN, the c-type lectin receptor signalling pathway responded uniquely in TF and TR. In response to stimulation with both immune mimics, TR responded more strongly than other groups. Further, group-specific pathway responses to PGN stimulation included NOD-like receptor signalling in W and platelet activation in TR. TF consistently showed the most attenuated immune response relative to W, and more DEGs were apparent in TR than TF and D relative to W, suggesting that a non-satiating ration coupled with elevated circulating GH levels may cause TR to possess enhanced immune capabilities. Alternatively, TF and D salmon are prevented from acquiring the same level of immune response as TR due to direction of energy to high overall somatic growth. Further study of the effects of ration restriction in growth-modified fishes is warranted. Conclusions: These findings improve our understanding of the pleiotropic effects of growth modification on the immunological responses of fish, revealing unique immune pathway responses depending on the mechanism of growth acceleration and nutritional availability. [ABSTRACT FROM AUTHOR]

Peptidoglycan recognition proteins (PGRPs) are a family of pattern recognition receptors (PRRs) involved in host antibacterial responses, and their functions have been characterized in most invertebrate and vertebrate animals. However, little information is available regarding the function of frog PGRPs. In this study, a short-type PGRP (termed Xl-PGRP-S) gene was identified in the African clawed frog, Xenopus laevis. The predicted protein of Xl-PGRP-S contains several structural features known in PGRPs, including a typical PGRP domain and two closely spaced conserved cysteines. Xl-PGRP-S gene was constitutively expressed in all tissues examined, with the highest expression level observed in muscle. As a typical PRR, Xl-PGRP-S is inducible after peptidoglycan (PGN) stimulation, and has an ability to bind PGN. In addition, Xl-PGRP-S has been proven to have Zn2+-dependent amidase activity and antibacterial activity against Edwardsiella tarda. The present study represents the first discovery on the function of frog PGRPs, thus contributing to a better understanding of the functional evolution of PGRPs in early tetrapods. • A short-type peptidoglycan recognition protein (PGRP), named as Xl-PGRP-S was identified in Xenopus laevis. • Xl-PGRP-S was predicted to have a PGRP domain and two conserved cysteine. • Xl-PGRP-S is expressed in various organs/tissues of the frog and also in A6 cells. • Xl-PGRP-S can bind with PGN and is inducible following PGN stimulation. • Zn2+-dependent amidase activity and antibacterial activity were observed for Xl-PGRP-S. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria (LAB) have long been used in the manufacture of yogurt and cheese. LAB inhabit the human gastrointestinal tract alongside dozens of varieties of gut bacteria, which play an essential role in modulating the innate immune response to gastrointestinal disorders. This research sought to provide a basis for the investigation of peptidoglycan (PGN) from Lactobacillus acidophilus (L. acidophilus) by macrophages phagocytosis related to the anti-inflammatory effect both in vitro and vivo. Results show that PGN, PGN hydrolysate and PGN monomer N-acetylmuramic acid (NAM) from L. acidophilus were found to have an anti-inflammatory effect on LPS-induced inflammation in RAW 264.7 cells, the profiling of iNOS mRNA levels was also inhibited in NAM-treated (100–300 µg/mL) group. The activation of the Nuclear factor κB (NF-κB) pathway is regulated by the cellular kinase p38 in mitogen-activated protein kinases (MAPK) upon NAM treatment (300 µg/mL). These findings were further supported in Escherichia coli (E. coli)-stimulated ICR mice, in which we found that oral administration of free L. acidophilus PGN and NAM from L. acidophilus exerted a potential anti-inflammatory response. NAM, as the main components of the LAB cell wall, will be a candidate for pharmaceutical application of anti-inflammatory drugs.

Eastern Kalahari languages are spoken in the eastern parts of Botswana along the eastern fringes of the Kalahari Desert. These languages are closely related to the well-known and documented languages Gǀui and Gǁana which are spoken in the west. From a historical linguistic perspective, Eastern Kalahari Khoe languages form a dialectal continuum within themselves and within Gǀui and Gǁana. In this continuum, several features in the domains of phonetics/phonology and morpho-syntax are reduced from west to east. Clicks are missing or modified in some cognates, and this variation is observed from the western dialects to the eastern ones: (i) nǂɂũũ (western) → niũũ (eastern) ‘eat’ gǃãĩ (western) → gãĩ (eastern) ‘ibex’ Morpho-syntactically, the presence of person-gender-number markers (PGNs) varies from the western dialects to the eastern ones: (ii) Kie kwa aba sa mũũ 1SG PROG. dog PGN-fem. see ‘I see a dog’ (female) [western] (iii) Cie kwa apa mũũ 1SG PROG. dog see ‘I see a dog’ (gender unspecified) [eastern] Some phonetic or phonological features, such as delayed aspiration, are modified while others are introduced, such as tonal depression. This paper will examine click loss, PGN attrition and other syntactic features and variations within this zone. Systematic comparisons of these linguistic features will be presented and appropriate analyses of processes discussed with a view to account for the (non-)occurrences of these features in this dialectal continuum. While language contact phenomena may precipitate some of these feature losses, it is the thesis of the paper that there is an apparent regularity in some of these morpho-syntactic variations. The ultimate aim of this paper is to answer the question, “What have these languages lost linguistically?”

Emergence of drug resistance during visceral leishmaniasis (VL) is a major obstacle imposed during successful therapy. An effective vaccine strategy against this disease is therefore necessary. Our present study exploited the SLA (soluble leishmanial antigen) and PGN (peptidoglycan) stimulated bone marrow-derived dendritic cells (DCs) as a suitable vaccine candidate during experimental VL. SLA-PGN-stimulated DCs showed a significant decrease in hepatic and splenic parasite burden, which were associated with increased production of nitric oxide and pro-inflammatory cytokines such as IL-12, IFN-γ and IL-17. Elevated level of IL-17 was accompanied with the generation of more Th17 cells. Further studies on DC provided the evidence that these SLA-PGN-stimulated DCs played an important role in providing necessary cytokines such as IL-6, IL-23 and TGF-β for the generation of Th17 cells. Interestingly, inhibition of protein kinase C-β (PKCβ) in DCs led to decreased production of Th17 polarizing cytokines, causing reduction of the Th17 population size. Altogether, our finding highlighted the important role of DC-based PKCβ in regulation of the function and generation of Th17 cells. [ABSTRACT FROM AUTHOR]

Tumor-induced host wasting and mortality are general phenomena across species. Many groups have previously demonstrated endocrinal impacts of malignant tumors on host wasting in rodents and Drosophila. Whether and how environmental factors and host immune response contribute to tumor-associated host wasting and survival, however, are largely unknown. Here, we report that flies bearing malignant yki3SA-gut tumors exhibited the exponential increase of commensal bacteria, which were mostly acquired from the environment, and systemic IMD-NF-κB activation due to suppression of a gut antibacterial amidase PGRP-SC2. Either gut microbial elimination or specific IMD-NF-κB blockade in the renal-like Malpighian tubules potently improved mortality of yki3SA-tumor-bearing flies in a manner independent of host wasting. We further indicate that renal IMD-NF-κB activation caused uric acid (UA) overload to reduce survival of tumor-bearing flies. Therefore, our results uncover a fundamental mechanism whereby gut commensal dysbiosis, renal immune activation, and UA imbalance potentiate tumor-associated host death. [Display omitted] • Fly yki3SA-gut tumors cause bacterial overload via suppression of gut PGRP-SC2 • Gut bacterial clearance increases survival of yki3SA-tumor-bearing flies • Renal-specific IMD-NF-κB blockade increases survival of yki3SA-tumor-bearing flies • Renal IMD-NF-κB blockade diminishes yki3SA-tumor-associated uric acid accumulation How host immune responses contribute to tumor-associated wasting or mortality is unknown. Chen et al. show that Drosophila yki3SA-gut tumors suppress PGRP-SC2 production to cause gut bacterial overload and systemic IMD-NF-κB activation, promoting host death without affecting wasting. They demonstrate that renal IMD-NF-κB-mediated uric acid accumulation increases host mortality. [ABSTRACT FROM AUTHOR]

Neonates heavily depend on the innate immune system for defence against invading pathogens. Toll-like receptors (TLRs) represent a primary line of host defence and play an important role in orchestrating the inflammatory response to invading pathogens. The most commonly infecting pathogens in neonates are E. coli, Klebsiella pneumoniae and Staphylococcus aureus. Also, co-infection with more than one organism is common in neonatal sepsis. Therefore, we aimed to study the TLR2 and TLR4 mediated neonatal inflammatory response to these pathogens. For this, we stimulated mononuclear cells from cord blood with LPS, PGN, E. coli, K.pneumoniae andS.aureus and analyzed the surface expression of TLR2 and TLR4 on CD14+CD16+ and CD14dimCD16+ and its inflammatory response in comparison with peripheral blood. We found that the TLR2 and TLR4 were differentially expressed on both monocyte subpopulations. Cytokines such as IL-6, IL-1β, IL-23, IL-10, IL-13, MCP-1 and IL-8 were measured using ELISA and we observed that although, neonatal cells were able to produce similar levels of the classical pro-inflammatory (IL-6, IL-1β) and anti-inflammatory (IL-10, IL-13) cytokines as that of adult cells, the amounts of IL-23 and MCP-1 were lower in CBMCs while the chemokine IL-8 was higher in CBMCs when compared with PBMCs. In addition, using Human Inflammation Antibody array technique we found that multiple cytokine production was impaired in cord blood when cells were co-infected with LPS and PGN. In conclusion, the TLR-mediated inflammatory response to neonatal pathogens is differentially regulated by different pathogens. [ABSTRACT FROM AUTHOR]

CD6 is a lymphocyte glycoprotein receptor that physically associates with the antigen‐specific receptor complex at the center of the immunological synapse, where it interacts with its ligand CD166/ALCAM. The present work reports the carbohydrate‐dependent interaction of CD6 and CD166/ALCAM with Galectin‐1 and ‐3, two well‐known soluble mammalian lectins. Both galectins interfered with superantigen‐induced T cell proliferation and cell adhesion phenomena mediated by the CD6‐CD166/ALCAM pair, while CD6 expression protected cells from galectin‐induced apoptosis. The results suggest that interaction of Galectin‐1 and ‐3 with CD6 and CD166/ALCAM might modulate some relevant aspects of T cell physiology.Galectin‐1 and ‐3 are two new interacting proteins for CD6 and its ligand CD166/ALCAM. Galectin‐1 and ‐3 modulate T cell proliferation and adhesion involving CD6‐CD166/ALCAM. The intracellular region of CD6 has protective effects against galectin‐induced T cell apoptosis. The interaction of Galectin‐1 and ‐3 with CD6 has a modulatory effect on T cell physiology. [ABSTRACT FROM AUTHOR]

Pharyngitis is an inflammation of the pharynx caused by viral, bacterial, or non-infectious factors. In the present study, the anti-inflammatory efficacy of carvacrol was assessed using an in vitro model of streptococcal pharyngitis using human tonsil epithelial cells (HTonEpiCs) induced with Streptococcus pyogenes cell wall antigens. HTonEpiCs were stimulated by a mixture of lipoteichoic acid (LTA) and peptidoglycan (PGN) for 4 h followed by exposure to carvacrol for 20 h. Following exposure, interleukin (IL)-6, IL-8, human beta defensin-2 (HBD-2), epithelial-derived neutrophil-activating protein-78 (ENA-78), granulocyte chemotactic protein-2 (GCP-2), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and prostaglandin (PGE2) were measured by enzyme-linked immunosorbent assays (ELISA). The levels of pro-inflammatory cytokines, IL-6, IL-8, ENA-78, and GCP-2 were decreased in a carvacrol dose-dependent manner. The production of HBD-2 was significantly suppressed over 24 h carvacrol treatments. PGE2 and COX-2 levels in the cell suspensions were affected by carvacrol treatment. TNF-α was not detected. The cell viability of all the tested carvacrol concentrations was greater than 80%, with no morphological changes. The results suggest that carvacrol has anti-inflammatory properties, and carvacrol needs to be further assessed for potential clinical or healthcare applications to manage the pain associated with streptococcal pharyngitis. [ABSTRACT FROM AUTHOR]

Plants are sessile organisms that are under constant attack from microbes. They rely on both preformed defenses, and their innate immune system to ward of the microbial pathogens. Preformed defences include for example the cell wall and cuticle, which act as physical barriers to microbial colonization. The plant immune system is composed of surveillance systems that perceive several general microbe elicitors, which allow plants to switch from growth and development into a defense mode, rejecting most potentially harmful microbes. The elicitors are essential structures for pathogen survival and are conserved among pathogens. The conserved microbe-specific molecules, referred to as microbe- or pathogen-associated molecular patterns (MAMPs or PAMPs), are recognized by the plant innate immune systems pattern recognition receptors (PRRs). General elicitors like flagellin (Flg), elongation factor Tu (EF-Tu), peptidoglycan (PGN), lipopolysaccharides (LPS), Ax21 (Activator of XA21-mediated immunity in rice), fungal chitin, and p-glucans from oomycetes are recognized by plant surface localized PRRs. Several of the MAMPs and their corresponding PRRs have, in recent years, been identified. This review focuses on the current knowledge regarding important MAMPs from bacteria, fungi, and oomycetes, their structure, the plant PRRs that recognizes them, and how they induce MAMP-triggered immunity (MTI) in plants. [ABSTRACT FROM AUTHOR]

Abstract: The mechanisms and molecular effectors of pathogen recognition systems in diverse hosts are highly conserved. Both plant and animal recognition of pathogens relies on sensing of Pathogen-Associated Molecular Patterns (PAMPs) by Pattern Recognition Molecules (PRMs). To detect bacteria, these sensor molecules can recognize a wide array of molecules ranging from lipopolysaccharides (LPS) to peptidoglycan (PGN) or proteins. In contrast to that of mammals, the repertoire of bacterial motifs recognized by the immune system of the fruit fly seems to be much narrower. Works published so far indicate that it is limited to bacterial PGN and its derivatives. The mode of detection of PGN by host proteins is also simpler in the fly immune system than it is in the mammalian counterpart. Although PGN can be detected by Toll-like receptors, Nucleotide-binding oligomerization domain proteins and Peptidoglycan Recognition proteins (PGRPs) in vertebrates, PGRP family members are, so far, the only PGN sensors identified in Drosophila. Interactions between PGN and PGRPs induce multiple processes required to mount a specific and is implicated in multiple processes require to induce a specific and fine-tuned bacterial immune response in fly. Here, we present an overview of our current knowledge of PGRP and their bacterial detection in Drosophila. [Copyright &y& Elsevier]

The symbiotic relationship between commensal microbes and host animals predicts unidentified beneficial impacts of individual bacterial metabolites on animal physiology. Peptidoglycan fragments (muropeptides) from the bacterial cell wall are known for their roles in pathogenicity and for inducing host immune responses. However, the potential beneficial usage of muropeptides from commensal bacteria by the host needs exploration. We identified a striking role for muropeptides in supporting mitochondrial homeostasis, development, and behaviors in Caenorhabditis elegans. We determined that the beneficial molecules are disaccharide muropeptides containing a short AA chain, and they enter intestinal-cell mitochondria to repress oxidative stress. Further analyses indicate that muropeptides execute this role by binding to and promoting the activity of ATP synthase. Therefore, given the exceptional structural conservation of ATP synthase, the role of muropeptides as a rare agonist of the ATP synthase presents a major conceptual modification regarding the impact of bacterial cell metabolites on animal physiology. [Display omitted] • Bacterial PG muropeptides support C. elegans development and food behavior • PG muropeptides suppress host mitochondrial oxidative stress • PG muropeptides accumulate in host intestinal mitochondria • PG muropeptides bind to and act as agonists of ATP synthase Tian and Han report a role for bacterial cell wall-derived peptidoglycan muropeptides in promoting development and food-seeking behavior in C. elegans. The study suggests that these beneficial muropeptides enter host intestinal mitochondria and bind to ATP synthases, preventing oxidative stress and promoting mitochondrial homeostasis. [ABSTRACT FROM AUTHOR]

Summary: Although the JAK/STAT signaling pathway is usually involved in antiviral defense, a recent study suggested that STAT might be annexed by WSSV (white spot syndrome virus) to enhance the expression of a viral immediate early gene in infected shrimps. In the present study, we clone and report the first full-length cDNA sequence for a crustacean STAT from Penaeus monodon. Alignment and comparison with the deduced amino acid sequences of other STATs identified several important conserved residues and functional domains, including the DNA binding domain, SH2 domain and C-terminal transactivation domain. Based on these conserved sequences, a phylogenetic analysis suggested that shrimp STAT belongs to the ancient STAT family, while the presence of the functional domains suggested that shrimp STAT might share similar functions and regulating mechanisms with the well-known STATs isolated from model organisms. Real-time PCR showed a decreased transcription level of shrimp STAT after WSSV infection, but a Western blot analysis using anti-phosphorylated STAT antibody showed an increased level of phosphorylated (activated) STAT in the lymphoid organ of shrimp after WSSV infection. We further show that a primary culture of lymphoid organ cells from WSSV-infected shrimp resulted in activated STAT being translocated from the cytoplasm to the nucleus. This report provides experimental evidence that shrimp STAT is activated in response to WSSV infection. Our results support an earlier finding that WSSV does not disrupt JAK/STAT pathway, but on the contrary benefits from STAT activation in the shrimp host. [Copyright &y& Elsevier]

Este artículo examina el comportamiento del turismo en España, tanto nacional como internacional, analizando las principales macromagnitudes. Asimismo se precisan las preferencias espaciales de los turistas como los cambios comportamentales que han acaecido a lo largo del año 2002 con respecto al año 2001. También se indagan los efectos que sobre el empleo ha tenido el descenso en la llegada de viajeros a espacios concretos como Baleares.The changes in destinations and behaviour for these tourists along 2002 versus 2001 are presented as well as the impact on the labour forcé due to decrease of the number of tourists in some specifics places like Baleares.

Peptidoglycan recognition proteins (PGRPs), which are discovered in invertebrates and vertebrates, play an important role in antibacterial immunity. However, the function of PGRPs is largely uninvestigated in reptiles. In the present study, a short-type PGRP gene, designed as C-turtle-PGRP-S, was identified in the Chinese soft-shelled turtle, Pelodiscus sinensis. The C-turtle-PGRP-S contains a highly conserved PGRP domain and has close relationship with PGRP-S orthologues in other species according to sequence and phylogenetic analyses. C-turtle-PGRP-S gene was constitutively expressed in all detected tissues and was induced by Edwardsiella tarda. Additionally, recombinant C-turtle-PGRP-S showed PGN binding activity and antibacterial function against E. tarda. Therefore, it is suggested that the function of PGRP-S is likely to be conserved in reptile vertebrates, as observed in other vertebrates, shedding light on the evolutionary conservation of PGRPs. • A short-type PGRP gene was cloned in Chinese soft-shelled turtle, P. sinensis. • The PGRP-S has a conserved PGRP domain and is constitutively expressed. • The PGRP-S can bind PGN and LPS, and has amidase activity. • Antibacterial effect of PGRP-S is also observed. • The PGRP-S has conserved organization and function as in other vertebrates. [ABSTRACT FROM AUTHOR]

Injection of crude lipopolysaccharide (LPS) from Escherichia coli into the hemocoel of Biomphalaria glabrata stimulates cell proliferation in the amebocyte-producing organ (APO). However, it is not known if mitogenic activity resides in the lipid A or O-polysaccharide component of LPS. Moreover, the possible role of substances that commonly contaminate crude LPS and that are known to stimulate innate immune responses in mammals, e.g., peptidoglycan (PGN), protein, or bacterial DNA, is unclear. Therefore, we tested the effects of the following injected substances on the snail APO: crude LPS, ultrapurified LPS (lacking lipoprotein contamination), two forms of lipid A, (diphosphoryl lipid A and Kdo2-lipid A), O-polysaccharide, Gram negative PGN, both crude and ultrapurified (with and without endotoxin activity, respectively), Gram positive PGN, PGN components Tri-DAP and muramyl dipeptide, and bacterial DNA. Whereas crude LPS, ultrapurified LPS, and crude PGN were mitogenic, ultrapurified PGN was not. Moreover, LPS components, PGN components, and bacterial DNA were inactive. These results suggest that it is the intact LPS molecule which stimulates cell division in the APO., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The IMD pathway signaling plays a pivotal role in the Drosophila defense against bacteria. During the last two decades, significant progress has been made in identifying the components and deciphering the molecular mechanisms underlying this pathway, including the means of bacterial sensing and signal transduction. While these findings have contributed to the understanding of the immune signaling in insects, they have also provided new insights in studying the mammalian NF-κB signaling pathways. Here, we summarize the current view of the IMD pathway focusing on how it regulates the humoral immune response of Drosophila., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Innate immunity is the front line of self-defense against infectious non-self in vertebrates and invertebrates. The innate immune system is mediated by germ-line encoding pattern recognition molecules (pathogen sensors) that recognize conserved molecular patterns present in the pathogens but absent in the host. Peptidoglycans (PGN) are essential cell wall components of almost all bacteria, except mycoplasma lacking a cell wall, which provides the host immune system an advantage for detecting invading bacteria. Several families of pattern recognition molecules that detect PGN and PGN-derived compounds have been indentified, and the role of PGRP family members in host defense is relatively well-characterized in Drosophila. This review focuses on the role of PGRP family members in the recognition of invading bacteria and the activation and modulation of immune responses in Drosophila., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

C-type lectins are a family of Ca(2+)-dependent carbohydrate-binding proteins playing crucial roles in innate immunity of vertebrates and invertebrates. In the present study, the cDNA of a C-type lectin with one carbohydrate-recognition domain (CRD) of 127 amino acids was cloned from bay scallop Argopecten irradians (designated AiCTL-3) by rapid amplification of cDNA end (RACE) techniques based on expressed sequence tag (EST) analysis. The mRNA transcripts of AiCTL-3 could be detected in all the tested tissues including hepatopancreas, gonad, adductor muscle, heart, hemocytes, mantle and gill, with the highest expression level in hepatopancreas. After the challenges with Vibrio anguillarum and Micrococcus luteus, the mRNA expression level of AiCTL-3 was obviously up-regulated and reached the maximum level at 9h (11.87fold, P<0.01, and 20.02-fold, P<0.05, respectively). The recombinant AiCTL-3 (designated as rAiCTL-3) could bind LPS, PGN, and glucan in vitro, but could not bind mannan. And it also bound Gram-positive bacteria Staphylococcus aureus as well as Gram-negative bacteria Escherichia coli and V. anguillarum. With a Ca(2+) binding site 2 EPN (Glu-Pro-Asn) motif, rAiCTL-3 could bind both mannose and galactose which was quite different from those in vertebrate. Meanwhile, it could significantly enhance the phagocytosis of scallop hemocytes in vitro. The results clearly suggested that AiCTL-3 could serve not only as a PRR participated in the immune response against various PAMPs and bacteria in non-self recognition via mannose/galactose binding specificity but an opsonin playing an important part in clearance of invaders., (© 2013 Elsevier B.V. All rights reserved.)

The allograft inflammatory factor-1 (AIF-1) is one of the key factors associated with inflammatory response. In the present study, the full-length cDNA of AIF-1 was identified from Zhikong scallop Chlamys farreri (named as CfAIF-1) by EST (expressed sequence tag) analysis and RACE (rapid-amplification of cDNA ends) approaches. The cDNA of CfAIF-1 consisted of a 5-terminal untranslated region (UTR) of 58 bp, a 3-UTR of 607 bp with a poly (A) tail, and an open reading frame (ORF) of 468 bp encoding a polypeptide of 155 amino acids with the putative molecular mass of 17.8 kDa. There was an EF hand Ca(2+)-binding motif in the deduced amino acid sequence of CfAIF-1 which was conserved in other AIF-1s. CfAIF-1 shared closer phylogenetic relationship with invertebrate counterparts than vertebrate. The mRNA transcripts of CfAIF-1 were dominantly expressed in hepatopancreas, hemocytes and adductor. During scallop ontogenesis, the CfAIF-1 mRNA was expressed at a low level at early developmental stages from eggs to blastula, and then increased significantly from gastruta to late veliger larvae (P<0.05). Moreover, the mRNA expression levels of CfAIF-1 in the hemocytes of adult scallop were significantly up-regulated during 12-48 h after LPS, PGN and poly I:C stimulation (P<0.01), but there was no significant fluctuation detected after glucan stimulation. Furthermore, the challenge of bacteria Vibrio anguillarum remarkably induced the mRNA expression of CfAIF-1 in hemocytes at 6h (P<0.05) and 12h (P<0.01). All these results collectively indicated that CfAIF-1 might be involved in the immune response during the ontogenesis and contribute to the defense against microbe infection in scallops., (© 2013 Elsevier B.V. All rights reserved.)

Despite the well known role of nucleotide oligomerization domain (NOD) receptor proteins in innate immunity, their association with diabetes is less explored. Here we report the transcriptional level of NODs and their downstream molecular signatures in CD14(+) monocytes from subjects with different grades of glucose tolerance. NOD1 and NOD2 mRNA expression were significantly up-regulated in monocytes from patients with type 2 diabetes (T2DM) and positively correlated with HOMA-IR and poor glycemic control. Patients with T2DM also exhibited increased monocyte activation markers (CD11b and CD36) and proinflammatory signals downstream of NOD (RIPK2 and NFκB) along with the increased circulatory levels of TNF-α and IL-6. In vitro stimulation of monocytes with NOD specific ligands-i-EDAP and MDP significantly up regulated the mRNA expression of NOD1 and NOD2 respectively in T2DM. Our study exposes up regulation of NODs in monocytes as an important component of inflammation and insulin resistance in patients with T2DM., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Short peptidoglycan recognition protein (PGRP-S) is a member of the innate immunity system in mammals. PGRP-S from Camelus dromedarius (CPGRP-S) is found to be highly potent against bacterial infections. It is capable of binding to a wide range of pathogen-associated molecular patterns (PAMPs) including lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PGN). The heparin-like polysaccharides have also been observed in some bacteria such as the capsule of K5 Escherichia coli thus making them relevant for determining the nature of their interactions with CPGRP-S. The binding studies of CPGRP-S with heparin disaccharide in solution using surface plasmon resonance gave a value 3.3×10(-7) M for the dissociation constant (Kd). The structure of the heparin bound CPGRP-S determined at 2.8Å resolution revealed the presence of a bound heparin molecule in the binding pocket of CPGRP-S. It was found anchored tightly to the protein with the help of several ionic and hydrogen bonded interactions. Three sulphate groups of heparin S1, S2 and S3 have been found to interact with residues, Arg-31, Lys-90, Thr- 97, Asn-99 Asn-140, Gln-150 and Arg-170 of CPGRP-S. The binding site includes two subsites, S-I and S-II with cleft-like structures. Heparin disaccharide is bound in subsite S-I. Previously determined structures of the complexes of CPGRP-S with LPS, LTA and PGN also showed that their glycan moieties were also held in subsite S-I indicating that heparin disaccharide also represents an important element for the recognition by CPGRP-S.