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Abstract: We present detailed results on the C4-HSL-mediated quorum sensing (QS) regulatory system of the opportunistic Gram-negative bacterium Aeromonas hydrophila. This bacterium contains a particularly simple QS system that allows for a detailed modeling of kinetics. In a model system (i.e., the Escherichia coli monitor strain MH205), the C4-HSL production of A. hydrophila is interrupted by fusion of gfp(ASV). In the present in vitro study, we measure the response of the QS regulatory ahyRI locus in the monitor strain to predetermined concentrations of C4-HSL signal molecules. A minimal kinetic model describes the data well. It can be solved analytically, providing substantial insight into the QS mechanism: at high concentrations of signal molecules, a slow decay of the activated regulator sets the timescale for the QS regulation loop. Slow saturation ensures that, in an A. hydrophila cell, the QS system is activated only by signal molecules produced by other A. hydrophila cells. Separate information on the ahyR and ahyI loci can be extracted, thus allowing the probe to be used in identifying the target when testing QS inhibitors. [Copyright &y& Elsevier]

Bacteria communicate with each other by a process termed “quorum sensing” (QS), and diffusible, low-molecular-weight chemicals, called signal molecules, are used as the communication languages. In cell-free Burkholderia cepacia CF-66 culture supernatants, five compounds suspected of being signal molecules were identified. The gene ( cepI) related with AHLs synthesis were not detected by polymerase chain reaction (PCR) using specific primers. Gas chromatography–mass spectrometry (GC–MS) revealed that these compounds were not AHLs but the diketopiperazines (DKPs) cyclo(Pro–Phe), cyclo(Pro–Tyr), cyclo(Ala–Val), cyclo(Pro–Leu), and cyclo(Pro–Val), all of which were both d and l-type. Four kinds of DKPs had been isolated from other Gram-negative bacteria, but the other was a novel kind discovered in CF-66, and l-cyclo (Pro–Phe) was quantified by GC–MS. It was found that exogenous DKPs had a negative effect on the candidacidal activity of the culture supernatant extracts. [ABSTRACT FROM AUTHOR]

Abstract: Switching from single-cell (planktonic) to biofilm growth (and vice versa) is regulated by a variety of environmental and physiological cues. Signals leading to activation of stress responses often lead to biofilm formation which, in turn, can trigger induction of stress response mechanisms, suggesting direct cross-talk between the two cellular processes. Regulatory mechanisms of this process include two-component regulatory systems, master regulators such as the rpoS gene and signal molecules such as cyclic-di-GMP, in a tight and complex interplay. [Copyright &y& Elsevier]

Abstract: Under certain circumstances the individuals of a bacterial population may find advantages in acting together and making “collective decisions”. This phenomenon is better known as quorum sensing. When the concentration of signal molecules produced by the surrounding bacteria exceeds a certain threshold, the bacterial population acts as a single organism, collectively expressing virulence genes, biofilm forming genes, etc. Several mechanisms of quorum sensing are discussed, each with its distinct signal molecules and respective receptors. Some of these mechanisms are restricted to sensing intraspecies signalling, but interspecies and even interkingdom signalling have also been described. Several veterinary pathogens such as Staphylococcus aureus, Staphylococcus pseudintermedius, Pseudomonas aeruginosa and Salmonella Typhimurium use quorum sensing as a means to optimize virulence gene expression and host colonization. Therefore, targeting of the QS mechanisms may provide a novel strategy for combating bacterial infections, also in veterinary medicine. [Copyright &y& Elsevier]

Using thin-layer chromatography, 16 bacterial isolates from root nodules of 8 different Psoralea species were quantitatively assessed for their exudation of the metabolites lumichrome, riboflavin and IAA in response to pH, salinity and temperature. Our data showed that the bacterial strains tested differed in their levels of secretion of the three metabolites. For example, strain AS2 produced significantly greater amounts of lumichrome at both pH 5.1 and 8.1, while strains RT1 and PI produced more lumichrome per cell at only pH 8.1. Strains API and RP2 also produced more riboflavin at pH 5.1 than at pH 8.1; conversely strain RTl secreted more riboflavin at pH 8.1 than at pH 5.1. Two P. repens strains (RP1 and RP2) isolated from very saline environments close to the Indian Ocean produced significant levels of lumichrome and riboflavin at both low and high salinity treatments. However, strains ACI and LI (from P. aculeata and P. laxa) even produced greater amounts of lumichrome and riboflavin at higher salinity (i.e. 34.2 mM NaCl) and probably originated from naturally saline soils. In this study, high acidity and high temperature induced the synthesis and release of high levels of IAA by bacterial cells. In contrast, there was greater strain secretion of lumichrome at lower temperature (10°C) than at high temperature (30°C). The variations in the secretion of lumichrome, riboflavin and IAA by bacterial strains exposed to different pH, salinity and temperature regimes suggest that genes encoding these metabolites are regulated differently by the imposed environmental factors. The data from this study also suggest that natural changes of pH, salinity and/or temperature in plant rhizospheres could potentially elevate the concentrations of lumichrome, riboflavin and IAA in soils. An accumulation of these molecules in the rhizosphere would have consequences for ecosystem functioning as both lumichrome and riboflavin have been reported to act as developmental signals that affect species in all three plant, animal, and microbial kingdoms. [ABSTRACT FROM AUTHOR]

Abstract: In Paramecium primaurelia mating interactions take place immediately after mixing mating-competent cells of opposite mating types. The cells clump in clusters (mating reaction) and then separate in pairs. Previous results have shown that sialic acid-containing glycoconjugates are present on the cell surface and are involved in mating-cell pairing. In order to identify the sialic acid-containing glycoprotein(s), we first metabolically radiolabelled non-mating-competent cells with d-[6-3H]galactose, and then analyzed the radiolabelled proteins by anion exchange chromatography. We characterized a 38kDa (gp38) sialic acid-containing glycoprotein and raised the corresponding polyclonal antibody by means of which we localized the antigen at the level of the oral region of non-mating-competent cells and on the ciliary surface of mating-competent cells. Immunoblot analysis of the ciliary protein fraction showed that the anti-gp38 serum interacted with a 38kDa protein in both mating types I and II cells. We also demonstrated the functional activity of gp38 in the mating reaction by means of anti-gp38 antibody competition assays. [Copyright &y& Elsevier]

No clear data are available on how flavonoids from different chemical groups affect root colonization by arbuscular mycorrhizal fungi (AMF) and whether flavonoids affecting the presymbiotic growth of AMF also affect root colonization by AMF. In the present work, we compared the effect of flavones (chrysin and luteolin) and flavonols (kaempferol, morin, isorhamnetin, and rutin) on root colonization (number of entry points and degree of root colonization) of tomato plants (Lycopersicum esculentum L.) with the effect of these flavonoids on the presymbiotic growth of these AMF, which has been reported in a recent study. With all tested AMF (Gigaspora rosea, Gigaspora margarita, Glomus mosseae, and Glomus intraradices) a correlation between the number of entry points and the percentage of root colonization was found. When the number of entry points was high, root colonization was also enhanced. Application of the flavones chrysin and luteolin and of the flavonol morin increased the number of entry points and the degree of colonization,whereas the flavonols kaempferol, isorhamnetin, and rutin showed no effect. These results show that in contrast to their effect on the presymbiotic growth of the AMF on the level of root colonization, the tested flavonoids do not exhibit a genus- and species-specificity. Moreover, comparison of our data with the data obtained by J.M. Scervino, M.A. Ponce, R. Erra-Bassells, H. Vierheilig, J.A. Ocampo, and A. Godeas. (2005a. J. Plant Interact. 15: 22–30) indicates that a positive effect on the hyphal growth of AMF does not necessarily result in an enhanced AM root colonization, further indicating that the mode of action of flavonoids at the level of root colonization is more complex. [ABSTRACT FROM AUTHOR]

Abstract: Arbuscular mycorrhizal (AM) fungi are obligate symbionts that need their plant hosts to complete their life cycle. In the absence of the plant, germlings arrest growth after a few days and retract most of their cytoplasm back into the multinuclear spores. The spores can germinate again during more favorable conditions. How AM fungi recognize compatible host roots and activate their symbiotic program is not yet understood. However, research in this field in the last years has shed light into this topic. We, and others, have approached some of these aspects by studying changes in fungal gene expression observed at early stages of development, before and at the plant recognition stage in an attempt to identify genes and proteins featuring as key regulators in the switch between the asymbiotic and symbiotic style of life. The molecular bases of this recognition process are now starting to be understood and point to common signaling pathways shared with other microbe-plant associations and to arbuscular mycorrhiza specific signaling pathways. [Copyright &y& Elsevier]

Many Gram-negative bacteria use N-acyl homoserine lactones (AHLs) as quorum-sensing (QS) signal molecules. AHL QS has been the subject of extensive investigation in the last decade and has become a paradigm for bacterial intercellular signaling. Research in AHL QS has been considerably aided by simple methods devised to detect AHLs using bacterial biosensors that phenotypically respond when exposed to exogenous AHLs. This article reviews and discusses the currently available bacterial biosensors which can be used in detecting and studying the different AHLs. [ABSTRACT FROM AUTHOR]

The aim of this paper is to provide a review of the current understanding of the mechanisms, cell and factors required for regeneration and restoration of periodontal tissue around natural teeth. Periodontal regeneration is a complex multifactorial process involving cell populations: periodontal ligament cells, bone cells, gingival fibroblasts and epithelial cells. This paper describes bone graft, guided tissue regeneration and enamel matrix derivative with the application of growth factors. [ABSTRACT FROM AUTHOR]

Summary: The effect of flavonoids isolated from arbuscular mycorrhizal (AM) colonized and noncolonized clover roots on the number of entry points and percentage of root colonization of tomato (Lycopersicum esculentum L.) by Gigaspora rosea, Gi margarita, Glomus mosseae and G. intrarradices symbionts was determined. With fungi of both genera, a correlation between the number of entry points and the percentage of root colonization was found in the presence of some of the tested flavonoids. The flavonoids acacetin and rhamnetin, present in AM clover roots, inhibited the formation of AM penetration structures and the AM colonization of tomato roots, whereas the flavonoid 5,6,7,8,9-hydroxy chalcone, which could not be detected in AM clover root, inhibited both parameters. The flavonoid quercetin, which was present in AM clover roots, stimulated the penetration and root colonization of tomato by Gigaspora. However, the flavonoids 5,6,7,8-hydroxy-4′-methoxy flavone and 3,5,6,7,4′-hydroxy flavone, which was not found in AM clover root, increased the number of entry points and the AM colonization of tomato roots by Gigaspora. These results indicated that flavonoids could be implicated in the process of regulation of AM colonization in plant root, but its role is highly complex and depend not only on flavonoids, but also on AM fungal genus or even species. [Copyright &y& Elsevier]

Bone and nacre feature highly orchestrated biomineralised structures. They are calcified structures that share an intervening organic matrix laid by specialized cells, bone cells in vertebrates and epithelial mantle cells in molluscs. Organic framework provides a scaffold for crystallisation and directs mineralisation. Bone and shell likely undergo self-reparation when damaged, clues to the presence in these mineralised structures of signal molecules, targeting the cells involved in their renewal. In molluscs, calcium carbonate crystallise under two mineral polymorphs, aragonite or calcite. Sudo et al. [22] reported two exclusive proteins in the shell of a bivalvia molluscan, Pinctada fucata, MSI 60 in aragonite and MSI 31 in calcite. We built up specific antibodies and experimented immunohistochemistry in Haliotis. These tools revealed the presence of Pinctada-like proteins within Haliotis mantle cells, in a zonation consistent with shell matrix mineralisation control involvement. Another facet of matrix-mediated biomineralisation control arises from bone and nacre interactivity. In vivo experiments of nacre implantation in sheep and rabbit established the biocompatibilty of nacre and bone. The nacreous part from the shell of Pinctada, a bivalve mollusc, was implanted as bone device in sheep and showed that nacre passes bone acceptance. Nacre implants were not subjected to intolerance reaction and the recipient bone provided with nacre underwent a sequence of bone regeneration within an osteoprogenitor-rich cell layer. The water-soluble organic matrix was extracted from powdered nacre by a gentle non-decalcifiying process. Three mammalian cell types, fibroblasts (human), bone marrow stromal cells (rat) and pre-osteoblasts (mouse) were used to characterize in vitro the effect of nacre water-soluble matrix on mammal bone cell lineage. In vitro studies provided evidence for the presence, in nacre organic matrix, of signal molecules responsible for the recruitment ... [Copyright &y& Elsevier]

Cellular activities are regulated by intracellular signals initiated by stimulation from the external and internal environments. Different signal pathways are involved in the initiation of different cellular functions. In connection with cell proliferation in response to mitogenic stimulation, the dose-effect relationship of the magnitude of ³ H-TdR incorporation into lymphocytes after exposure to different concentrations of concanavalin A (Con A) showed an inverted U-shaped curve in the concentration range 2-30 µg/ml. In previous studies it has been observed that the stimulatory effect of Con A (5 µg/ml) on lymphocyte proliferation was potentiated by whole-body irradiation (WBI) with low dose [0.075 Gy) and suppressed by WBI with high dose (2 Gy). When different concentrations of corticosterone, ranging from 10-12 to 10-7 M, were added to the Con A-stimulated lymphocytes, low-concentration stimulation and high-concentration suppression of lymphocyte proliferation were demonstrated. In the presence of 5 × 10-12 M (subphysiological concentration) of corticosterone the proliferation of thymocytes and splenic T cells in response to Con A was further up-regulated after low-dose radiation. Low-dose radiation (0.075 Gy) caused lowering of serum ACTH and corticosterone concentration as well as down-regulated transcription of the hypothalamic proopiomelanocortin gene. The present paper intends to show that multiple neurohormonal factors, including the pineal gland and neurotransmiters, in addition to the hypothalamic-pituitary-adrenocortical axis, are involved in the stimulation of immune responses induced by low-dose ionizing radiation. The complex nature of the interrelationship between the intracellular signaling of lymphocytes and the neuroendocrine regulation after WBI is discussed [ABSTRACT FROM AUTHOR]

We previously reported that LePR cDNA isolated from a cDNA library prepared from shikonin-producing cells of Lithospermum erythrorhizon encodes pathogenesis-related 10 (PR10) protein [J. Plant Physiol. 155 (1999) 364]. Here, we report an analysis of changes in LePR1 gene expression in response to signal molecules in the plant defense response system. Pathogen infection with bacteria (Erwinia stewartii and Pseudomonas syringae) and fungi (Aspergillus nidulans and Penicillium funiculosum) strongly induced LePR1 transcripts in inoculated leaves and in systemically affected leaves. When leaves were mechanically wounded, LePR1 gene expression was also increased 12 h after wounding. To evaluate the involvement with various signal transduction mechanisms, global signal molecules were applied to the leaves. Salicylic acid and its analogues, aspirin and BTH, definitely induced transcription of the LePR1 gene. Following H2O2 application, LePR1 transcripts accumulated to high levels 18 h after treatment and in a concentration-dependent manner. LePR1 transcript levels were also increased in response to octadecanoid pathway intermediates and to treatments with ABA. Our results indicate that the LePR1 gene shows very extensive and sensitive responses to pathogen infection as well as defense-related signal molecules. [Copyright &y& Elsevier]

The synthesis of organoiron derivatives of biologically active flavonoids is described. Lithium enolates of functionalised protected acetophenones and metallated derivatives of substituted aromatic rings have been employed as nucleophiles in combination with tricarbonyl(η5-cyclohexadienyl)iron electrophiles. Products have been converted into flavonoid and chalcone derivatives. Enolates generated from protected flavanones have also been used in nucleophile addition reactions, and a one-pot in situ protection, nucleophile addition, deprotection sequence is reported. [Copyright &y& Elsevier]

Odontoblasts differentiate from the cells of the dental papilla, and it has been well-established that their differentiation in developing teeth is induced by the dental epithelium. In experimental studies, no other mesenchymal cells have been shown to have the capacity to differentiate into odontoblasts, indicating that the dental papilla cells have been committed to odontoblast cell lineage during earlier developmental stages. We propose that the advancing differentiation within the odontoblast cell lineage is regulated by sequential epithelial signals. The first epithelial signals from the early oral ectoderm induce the odontogenic potential in the cranial neural crest cells. The next step in the determination of the odontogenic cell lineage is the development of the dental papilla from odontogenic mesenchyme. The formation of the dental papilla starts at the onset of the transition from the bud to the cap stage of tooth morphogenesis, and this is regulated by epithelial signals from the primary enamel knot. The primary enamel knot is a signaling center which forms at the tip of the epithelial tooth bud. It becomes fully developed and morphologically discernible in the cap-stage dental epithelium and expresses at least ten different signaling molecules belonging to the BMP, FGF, Hh, and Wnt families. In molar teeth, secondary enamel knots appear in the enamel epithelium at the sites of the future cusps. They also express several signaling molecules, and their formation precedes the folding and growth of the epithelium. The differentiation of odontoblasts always starts from the tips of the cusps, and therefore, it is conceivable that some of the signals expressed in the enamel knots may act as inducers of odontoblast differentiation. The functions of the different signals in enamel knots are not precisely known. We have shown that FGFs stimulate the proliferation of mesenchymal as well as epithelial cells, and they may also regulate the growth of the cusps. We have proposed that the enamel knot signals also have important roles, together with mesenchymal signals, in regulating the patterning of the cusps and hence the shape of the tooth crown. We suggest that the enamel knots are central regulators of tooth development, since they link cell differentiation to morphogenesis. [ABSTRACT FROM AUTHOR]

The aim of this review is not so much to show the problem of neuroendocrine, neurophysiologic, and neurochemical mechanisms of the immune system regulation of the organism by brain (there is a great deal of literature about it), as to solve the problem of whether the brain itself is an immune organ, and also to define cellular, neurochemical, and immunological properties of the brain for its immune defense when the blood-brain barrier is not damaged in spite of the penetration of the infection to brain. The accumulated literary data on CNS interaction with the immune system, expression of several cytokines and their receptors in the neurons of human brain culture, in astrocytes and microglia, all testify to the existence of a brain immune system. Recently studies appeared on the expression of major histocompatibility complex in brain neurons. It does not exclude the possibility of expression of immunoglobulins (or immunoglobulin-like proteins) in brain cells. Data obtained by us on the biosynthesis of a number of known interleukins and new cytokines in neurosecretory neurons of hypothalamus (N.Paraventricularis and N.Supraopticus) demonstrate that neuroendocrine nuclei of the hypothalamus are the center for neuroendocrine and immune systems of brain. [ABSTRACT FROM AUTHOR]

[Display omitted] • Proliferation of filamentous bacteria was positively regulated by quorum sensing. • C 6 -HSL increased from 31.39 ± 3.52 to 125.29 ± 6.70 ng/g VSS during the bulking. • Expressions of hdtS , lasR , cciR genes significantly enhanced during the bulking. • Filamentous bulking was significantly inhibited by quorum sensing inhibitors. The microcosmic mechanisms underlying filamentous bulking are still unclear. Quorum sensing (QS) is an important mechanism by which bacteria control self-reproduction and growth in response to changes in population density. The potential role of QS in filamentous bulking and the feasibility of using a Quorum quenching (QQ) strategy to inhibit filamentous bulking were investigated in this study. The results indicated that the rate of increase in the population density and the abundance of filamentous bacteria in the serious filamentous bulking stage (250 mL/g < SVI) was 1.46 and 2.76 times greater, respectively, than that of the limited filamentous bulking stage (150 mL/g < SVI < 250 mL/g). The proliferation of filamentous bacteria was clearly population density-dependent. The concentration of C 6 -HSL increased from 31.39 ± 3.52 ng/g VSS to 125.29 ± 6.70 ng/g VSS with an increase in the abundance of filamentous bacteria. Filamentous bulking could be promoted by exogenous N-acyl homoserines (AHLs), especially C 6 -HSL. The hdtS gene related to the synthesis of AHLs and the lasR and cciR genes related to receptors showed significantly increased expressions during filamentous bulking. SDHA, ND1, and CDK2 genes related to proliferation showed significantly increased expression during filamentous bulking. The QS-AHL system was triggered during filamentous bulking, which promoted the proliferation of filamentous bacteria. As expected, filamentous bulking was significantly inhibited by the addition of vanillin, a quorum sensing inhibitor. Therefore, QQ is a potential strategy for the prevention and control of filamentous bulking. This study provides new information regarding the microcosmic mechanisms of filamentous bulking. [ABSTRACT FROM AUTHOR]

[Display omitted] • Various molalities of 3O-C6-HSL were added to calcified AnGS to recover activity. • 1 μM 3O-C6-HSL had the best effect on the activity recovery of calcified AnGS. • 3O-C6-HSL increased the sludge pore size and the performance of calcified AnGS. • The mechanism for recovering the activity of calcified AnGS was determined. Microbiota quorum sensing (QS) induced by 3O-C6-HSL (N-(β-ketocaproyl)-DL-homoserine lactone) inhibited the calcification of anaerobic granular sludge (AnGS), and the mechanism of promoting the activity recovery of calcified AnGS was studied in this paper. Through research, it was speculated that 3O-C6-HSL acted on calcified AnGS residual microorganisms to trigger QS. It enriched many functional microorganisms. For example, it promoted the growth of Methanospirillum. The CO 2 could be consumed quickly by Methanospirillum and reduced the calcium carbonate formation. The increase of microbial biomass would promote the activity of sludge. What's more, the pore size and porosity of sludge would increase, so the mass transfer channel will be broadened at same time. All those, could help the calcified AnGS quickly restore the activity and anaerobic system recover normal, which provided a new idea for the emergency rescue of anaerobic system in the future. [ABSTRACT FROM AUTHOR]

The prevention, early discovery and effective treatment of patients with hepatocellular carcinoma (HCC) remain a global medical challenge. At present, HCC is still mainly treated by surgery, supplemented by vascular embolization, radio frequency, radiotherapy, chemotherapy and biotherapy. The application of multikinase inhibitor sorafenib, chimeric antigen receptor T cells, or PD-1/PD-L1 inhibitors can prolong the median survival of HCC patients. However, the treatment efficacy is still unsatisfactory due to HCC metastasis and postoperative recurrence. During the process of hepatocyte malignant transformation, HCC tissues can express and secrete many types of specific biomarkers, or oncogenic antigen molecules into blood, for example, alpha-fetoprotein, glypican-3, Wnt3a (one of the key signaling molecules in the Wnt/β-catenin pathway), insulin-like growth factor (IGF)-II or IGF-I receptor, vascular endothelial growth factor, secretory clusterin and so on. In addition, combining immunotherapy with non-coding RNAs might improve anti-cancer efficacy. These biomarkers not only contribute to HCC diagnosis or prognosis, but may also become molecular targets for HCC therapy under developing or clinical trials. This article reviews the progress in emerging biomarkers in basic research or clinical trials for HCC immunotherapy., Competing Interests: Conflict-of-interest statement: The authors report no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Rhizobium etli is a microsymbiont of plants of the genus Phaseolus. Using mass spectrometry we have identified the lipo-chitin oligosaccharides (LCOs) that are produced by R. etli strain CE3. They are N-acetylglucosamine pentasaccharides of which the non-reducing residue is N-methylated and N-acylated with cis-vaccenic acid (C18:1) or stearic acid (C18:0) and carries a carbamoyl group at C4. The reducing residue is substituted at the C6 position with O-acetylfucose. Analysis of their biological activity on the host plant Phaseolus vulgaris shows that these LCOs can elicit the formation of nodule primordia which develop to the stage where vascular bundles are formed. The formation of complete nodule structures, including an organized vascular tissue, is never observed. Considering the very close resemblance of the R. etli LCO structures to those of R. loti (I. M. López-Lara, J. D. J. van den Berg, J. E. Thomas Oates, J. Glushka, B. J. J. Lugtenberg, H. P. Spaink, Mol Microbiol 15: 627-638, 1995) we tested the ability of R. etli strains to nodulate various Lotus species and of R. loti to nodulate P. vulgaris. The results show that R. etli is indeed able to nodulate Lotus plants. However, several Lotus species are only nodulated when an additional flavonoid independent transcription activator (FITA) nodD gene is provided. Phaseolus plants can also be nodulated by R. loti bacteria, but only when the bacteria contain a FITA nodD gene. Apparently, the type of nod gene inducers secreted by the plants is the major basis for the separation of Phaseolus and Lotus into different cross inoculation groups. [ABSTRACT FROM AUTHOR]

In plant embryogenesis, inductive interactions mediated by diffusable signal molecules are most likely of great importance. Evidence has been presented that at late globular stages in plant embryogenesis, perturbation of the polar auxin transport results in abberrant embryo morphology. Rhizobium lipooligosaccharides or Nod factors are a newly discovered class of bacterial molecules that are able to trigger initial steps in root nodule development in legumes. Part of the activity of Nod factors may be directed towards alteration of endogenous plant growth regulator balance. The same bacterial Nod factors promoted the formation of globular embryos in the carrot cell line ts11. Whether there exist plant analogues of the Nod factors and whether these molecules are active as a more universal control system perhaps designed to initiate and or mediate gradients in auxin and cytokinin remains to be determined. [ABSTRACT FROM AUTHOR]

Rhizobium bacteria produce certain lipo-oligosaccharides (modified chitin oligomers) after induction of nodulation ( nod) gene transcription by the host plant. The function of the rhizobial nod genes in the biosynthesis of these lipo-oligosaccharides, focusing on their host specific aspects, is discussed. The lipo-oligosaccharides can elicit various responses in the host plants, like the formation of pre-infection threads and nodule meristems. Speculating on their function in plant morphogenesis the question is raised: do the rhizobial lipo-oligosaccharides resemble unknown plant signal molecules? [ABSTRACT FROM AUTHOR]

• The entropy production rate per signal molecule is conserved in the nonlinear signal transduction system. • We obtained a condition in which the Onsager's reciprocity theorem holds even in the nonlinear signal transduction system. • Fluctuation circulation was newly introduced to describe the signal transduction amount. Cell signal transduction is an example of a nonequilibrium phenomenon. In this study, a nonequilibrium nonlinear thermodynamic model was formulated. First, we obtained a condition in which the Onsager's reciprocity theorem holds in the signal transduction. Second, it was found that the entropy production rate per signal molecule is conserved through signal transduction. Finally, it was determined that when Onsager's reciprocity theorem does not hold, fluctuation circulation is given by the phosphorylation rate of signal molecules. The simple relation implies that the fluctuation circulation can be an essential quantity of the signal transduction amount. These results expand the limit of nonequilibrium thermodynamics and can be used to provide ideas for signal transduction quantification. [ABSTRACT FROM AUTHOR]

Different aspects of the reciprocal regulatory influence on the development of gonadotropin-releasing hormone (GnRH)-producing- and immune systems in the perinatal ontogenesis and their functioning in adults in normal and pathological conditions are discussed. The influence of GnRH on the development of the immune system, on the one hand, and the influence of proinflammatory cytokines on the development of the hypothalamic-pituitary-gonadal system, on the other hand, and their functioning in adult offspring are analyzed. We have focused on the effects of GnRH on the formation and functional activity of the thymus, as the central organ of the immune system, in the perinatal period. The main mechanisms of reciprocal regulation of these systems are discussed. The reproductive health of an individual is programmed by the establishment and development of physiological systems during critical periods. Regulatory epigenetic mechanisms of development are not strictly genetically controlled. These processes are characterized by a high sensitivity to various regulatory factors, which provides possible corrections for disorders. [ABSTRACT FROM AUTHOR]

The membrane antifouling and shifts of microbial communities of long-term electric field applied in MBR (EMBR) for treating phenol wastewater was systematically investigated. The increased voltage increased the phenol degradation rate and slowed down the TMP increase rate in EMBR (G1–G4: 1.65 × 10−3–8.40 × 10−4 Mpa/d), indicated the enhancement of phenol treatment and mitigation of membrane fouling. Decrease of protein (PN)/polysaccharide (PS) in EPS increased the negative charge and decreased the hydrophobicity of sludge, thus abated its adsorption on membrane surface. The decrease of AHLs concentration attributed to the electrolysis of AHLs by the electro-generated H 2 O 2. Besides, the AHLs had significantly negative correlation with QQ bacteria Rhodococcus and Stenotrophomonas enrichment and positive correlation with QS bacteria Aeromonas decrease in EMBRs, suggesting that coupling effects of voltage and QQ bacteria degraded AHLs, thus decreased EPS content which was positively correlated with AHLs concentration. Biopolymer-degrading genera (Clostridium sensu strict etc.) increased in EMBR and on membrane surface, while biofilm-forming genera (Pseudomonas etc.) decreased on membrane surface. These resulted in EPS content decrease and membrane antifouling. Unlabelled Image • EMBR enhanced phenol treatment and mitigated membrane fouling. • Decrease of PN/PS in EPS abated the adsorption of sludge on membrane surface. • Decrease of EPS positively correlated with AHLs degradation in EMBR. • Coupling effects of electro-generated ROS and QQ bacteria degraded AHLs. • The applied voltage enriched biopolymer-degrading genera in EMBR and biofilm. [ABSTRACT FROM AUTHOR]

The formation of propagules is the critical stage for transmission of the pathogenic fungus Stemphylium eturmiunum. However, how the development of these propagules is regulated remains to be fully understood. Here, we show that nitric oxide (NO) is necessary for reproduction in S. eturmiunum.Application of NO scavenger carboxy-CPTIO (cPTIO) or soluble guanylate cyclase (sGC) inhibitor NS-2028 abolishes propagules formation, which was increased by a supplement of sodium nitroprusside (SNP). SNP supplement also triggered increased biosynthesis of melanin, which can be inhibited upon the addition of arbutin or tricyclazole, the specific inhibitors for DOPA and DHN synthetic pathway, respectively. Intriguingly, enhanced melanin biosynthesis corelates with an increased propagules formation; The SNP-induced increment propagules formation can be also compromised upon the supplement of cPTIO or NS-2028. RT-PCR analysis showed that SNP promoted transcription of brlA, abA and wetA at 0.2 mmol/L, but inhibited at 2 mmol/L. In contrast, SNP increased transcription of mat1, and mat2, and the synthetic genes for DHN and DOPA melanins at 2 mmol/L. However, the increased transcription of these genes is down-regulated upon the supplement of cPTIO or NS-2028. Thus, NO regulates reproduction and melanin synthesis in S. eturmiunum possibly through the NO-sGC-GMP signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Understanding microbial interactions in the methanogenesis system through quorum sensing (QS) is very important for system optimization. Known QS genes were collected and classified into seven groups based on the signal molecules, which were used for constructing a hierarchical quorum sensing database (QSDB). QSDB containing 39,981 QS genes of seven QS groups was constructed and QS genes were analyzed with QSDB. Methanogen genomes were aligned with QSDB and acyl-homoserine lactones (AHLs) system was predicted as the most probable QS system. This database was further applied to analyze QS in methanogens from two upflow anaerobic sludge blanket-anaerobic filter hybrid reactors with conductive filter (CFB) and nonconductive filter (SEP), and a control without filter (CON). The maximum COD degradation rates in CFB (722.2 ± 10.1 mg/L·h) was elevated by 42.9% compared to CON (505.4 ± 5.98 mg/L·h). Metagenomic sequencing revealed Methanosaeta, Methanobacterium, and Methanosarcina were dominant, and the abundances was 4.3 times higher in the sludge of CFB compared to CON. The overall abundance of QS genes was CFB > SEP > CON, and AHLs were the most abundant group of QS genes. The filI/filR system, a luxI/luxR homolog, was firstly detected in methanogens, showing a high abundance in the CFB (0.085%) compared to in the CON (0.058%). The concentration of AHL molecules in CFB biofilms (0.04%) was about four times that in the CON (0.01%). Syntrophobacter and Smithella were the two major syntrophic bacteria of methanogens, and their abundances were positively correlated with methanogens. In addition, Syntrophobacter and Smithella harbored QS RpfB (component of the diffusible signal factor system) and PDE (component of cyclic di-GMP system). This study provides useful guidance for deeply understanding of QS in anaerobic digestion systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In the present study, we examined the effect of cold-water swimming stress (CWSS) on plasma corticosterone levels. Mice were exposed to stress in 4°C for 3 mins. Plasma corticosterone (CORT) level was measured at 0, 15, and 30 min after stress stimulation. The plasma CORT level was gradually increased up to 30 min. Then we further examined the changes of several signaling molecules expression levels, such as p-ERK, p-JNK, p-P38, p-AMPKα1, p-AMPKα2, and p-mTOR, in the HPA axis. We observed that those signaling molecules were altered after stress in the HPA axis. p-ERK, p-JNK, p-P38, and p-mTOR proteins expression were reduced by CWSS in the HPA axis. However, the phosphorylation of AMPKα1 and AMPKα2 were activated after CWSS in the HPA axis. Our results suggest that the upregulation of plasma CORT level induced by CWSS may be modulated by the those signaling molecules., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Embryonic stem (ES) cells are a useful experimental material to recapitulate the differentiation steps of early embryos, which are usually invisible and inaccessible from outside of the body, especially in mammals. ES cells have greatly facilitated the analyses of gene expression profiles and cell characteristics. In addition, understanding the mechanisms during neural differentiation is important for clinical purposes, such as developing new therapeutic methods or regenerative medicine. As neurons have very limited regenerative ability, neurodegenerative diseases are usually intractable, and patients suffer from the disease throughout their lifetimes. The functional cells generated from ES cells in vitro could replace degenerative areas by transplantation. In this review, we will first demonstrate the historical views and widely accepted concepts regarding the molecular mechanisms of neural induction and positional information to produce the specific types of neurons in model animals. Next, we will describe how these concepts have recently been applied to the research in the establishment of the methodology of neural differentiation from mammalian ES cells. Finally, we will focus on examples of the applications of differentiation systems to clinical purposes. Overall, the discussion will focus on how historical developmental studies are applied to state-of-the-art stem cell research., (© 2021 Japanese Society of Developmental Biologists.)

Microbes respond to environmental stimuli through complicated signal transduction systems. In microbial biofilms, because of complex multiple species interactions, signals transduction systems are of an even higher complexity. Here, we performed a signal-molecule-treatment experiment to study the role of different signal molecules, including N-hexanoyl-L-homoserine lactone (C6-HSL), N-dodecanoyl-L-homoserine lactone (C12-HSL), Pseudomonas quinolone signal (PQS), and cyclic di-GMP (c-di-GMP), in the development of marine biofilms. Comparative metagenomics suggested a distinctive influence of these molecules on the microbial structure and function of multi-species biofilm communities in its developing stage. The PQS-treated biofilms shared the least similarity with the control and initial biofilms. The role of PQS in biofilm development was further explored experimentally with the strain Erythrobacter sp. HKB8 isolated from marine biofilms. Comparative transcriptomic analysis showed that 314 genes, such as those related to signal transduction and biofilm formation, were differentially expressed in the untreated and PQS-treated Erythrobacter sp. HKB8 biofilms. Our study demonstrated the different roles of signal molecules in marine biofilm development. In particular, the PQS-based signal transduction system, which is frequently detected in marine biofilms, may play an important role in regulating microbe-microbe interactions and the assemblage of biofilm communities., (Copyright © 2020 Wang, Ding, Long, Lan, Tong, Saha, Wong, Sun, Li, Zhang and Qian.)

Introduction: Pseudomonas aeruginosa is considered a dangerous pathogen, as it causes many human diseases, besides that it is resistant to almost all types of antibacterial agents. So, new strategies to overcome P. aeruginosa infection have evolved to attenuate its virulence factors and inhibit its quorum-sensing (QS) activity., Purpose: This study investigated the effect of tyrosol and EDTA as anti-quorum-sensing and antivirulence agents against P. aeruginosa PAO1., Methods: Anti-quorum activity of sub-minimum inhibitory concentrations (sub-MICs) of tyrosol and EDTA was tested using Chromobacterium violaceum (CV 12,472) biosensor bioassay. Miller assay was used to assess the inhibition of QS signal molecules by β-galactosidase activity determination. Also, their effects on the production of protease, lipase, lecithinase, and motility were tested. The inhibitory effects of these molecules on QS regulatory genes and exotoxins genes expression were evaluated by real-time PCR., Results: Tyrosol and EDTA at sub-MICs inhibited the production of violacein pigment. Both compounds inhibited QS molecules production and their associated virulence factors (protease, lipase, lecithinase, and motility) (P≤ 0.05). Besides, the expression levels of QS regulatory genes ( lasI, lasR, rhƖI, rhIR, pqsA, and pqsR ) and exotoxins genes ( exoS and exoY ) were significantly reduced (P≤ 0.05)., Conclusion: Both tyrosol and EDTA can be used to fight P. aeruginosa infection as anti-quorum-sensing and antivirulence agents at their sub-MICs., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Abdel-Rhman et al.)

Pristinamycin biosynthesis in Streptomyces pristinaespiralis is governed by a complex hierarchical signaling cascade involving seven different transcriptional regulators (SpbR, PapR1, PapR2, PapR3, PapR4, PapR5, and PapR6). The signaling cascade is triggered by γ-butyrolactone (GBL)-like effector molecules, whereby the chemical structure of the effector, as well as its biosynthetic origin is unknown so far. Three of the pristinamycin transcriptional regulators (SpbR, PapR3, and PapR5) belong to the type of γ-butyrolactone receptor (GBLR). GBLRs are known to either act as "real" GBLRs, which bind GBLs as ligands or as "pseudo" GBLRs binding antibiotics or intermediates thereof as effector molecules. In this study, we performed electromobility shift assays (EMSAs) with SpbR, PapR3, and PapR5, respectively, in the presence of potential ligand samples. Thereby we could show that all three GBLRs bind synthetic 1,4-butyrolactone but not pristinamycin as ligand, suggesting that SpbR, PapR3, and PapR5 act as "real" GBLRs in S. pristinaespiralis . Furthermore, we identified a cytochrome P450 monooxygenase encoding gene snbU as potential biosynthesis gene for the GBLR-interacting ligand. Inactivation of snbU resulted in an increased pristinamycin production, which indicated that SnbU has a regulatory influence on pristinamycin production. EMSAs with culture extract samples from the snbU mutant did not influence the target binding ability of SpbR, PapR3, and PapR5 anymore, in contrast to culture supernatant samples from the S. pristinaespiralis wild-type or the pristinamycin deficient mutant papR2::apra , which demonstrates that SnbU is involved in the synthesis of the GBLR-interacting ligand., (Copyright © 2020 Handel, Kulik and Mast.)

Objective: Fusarium oxysporum is a common pathogenic fungus in ginseng cultivation. Both pathogens and antagonistic fungi have been reported to induce plant resistance responses, thereby promoting the accumulation of secondary metabolites. The purpose of this experiment is to compare the advantages of one of the two fungi, in order to screen out more effective elicitors. The mechanism of fungal elicitor-induced plant resistance response is supplemented., Methods: A gradient dilution and the dural culture were carried out to screen strains. The test strain was identified by morphology and 18 s rDNA. The effect of different concentrations (0, 50, 100, 200, 400 mg/L) of Penicillium sp. YJM-2013 and F. oxysporum on fresh weight and ginsenosides accumulation were tested. Signal molecules transduction, expression of transcription factors and functional genes were investigated to study the induction mechanism of fungal elicitors., Results: Antagonistic fungi of F. oxysporum was identified as Penicillium sp. YJM-2013, which reduced root biomass. The total ginsenosides content of Panax ginseng adventitious roots reached the maximum (48.95 ± 0.97 mg/g) treated with Penicillium sp. YJM-2013 at 200 mg/L, higher than control by 2.59-fold, in which protopanoxadiol-type ginsenosides (PPD) were increased by 4.57 times. Moreover, Penicillium sp. YJM-2013 activated defense signaling molecules, up-regulated the expression of PgWRKY 1, 2, 3, 5, 7, 9 and functional genes in ginsenosides synthesis., Conclusion: Compared with the pathogenic fungi F. oxysporum , antagonistic fungi Penicillium sp. YJM-2013 was more conducive to the accumulation of ginsenosides in P. ginseng adventitious roots. Penicillium sp. YJM-2013 promoted the accumulation of ginsenosides by intensifying the generation of signal molecules, activating the expression of transcription factors and functional genes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

A wide range of prokaryotes produce and excrete bacteriocins (proteins with antimicrobial activity) to reduce competition from closely related strains. Application of bacteriocins is of great importance in food industries, while little research has been focused on the agricultural potential of bacteriocins. A number of bacteriocin producing bacteria are members of the phytomicrobiome, and some strains are plant growth promoting rhizobacteria (PGPR). Thuricin 17 is a single small peptide with a molecular weight of 3.162 kDa, a subclass IId bacteriocin produced by Bacillus thuringiensis NEB17, isolated from soybean nodules. It is either cidal or static to a wide range of prokaryotes. In this way, it removes key competition from the niche space of the producer organism. B. thuringiensis NEB17 was isolated from soybean root nodules, and thus is a member of the phytomicrobiome. Interestingly, thuricin 17 is not active against a wide range of rhizobial strains involved in symbiotic nitrogen fixation with legumes or against other PGPR. In addition, it stimulates plant growth, particularly in the presence of abiotic stresses. The stresses it assists with include key ones associated with climate change (drought, high temperature, and soil salinity). Hence, in the presence of stress, it increases the size of the overall niche space, within plant roots, for B. thuringiensis NEB17. Through its anti-microbial activity, it could also enhance plant growth via control of specific plant pathogens. None of the isolated bacteriocins have been examined as broadly as thuricin 17 on plant growth promotion. Thus, this review focuses on the effect of thuricin 17 as a microbe to plant signal that assists crop plants in managing stress and making agricultural systems more climate change resilient., (Copyright © 2020 Nazari and Smith.)

The type VI secretion system (T6SS) is a toxic effector delivery apparatus widely distributed in Gram-negative bacteria. The opportunistic pathogen Pseudomonas aeruginosa encodes three T6SSs, namely H1-, H2-, and H3-T6SS. Each T6SS possesses its own effectors and their roles are not yet fully understood. Here, we report that an H3-T6SS deletion mutant PAO1(Δ clpV3 ) significantly affected the virulence-related phenotypes including pyocyanin production, biofilm formation, proteolytic activity, and motilities. Most interestingly, the expression of T3SS genes was markedly affected, indicating a link between H3-T6SS and T3SS. RNA-Sequencing was performed to globally identify the genes differentially expressed when H3-T6SS was inactivated and the results obtained correlated well with the observed phenotypes. Interestingly, the expressions of T2SS, T3SS, H2-T6SS, and H3-T6SS were all significantly decreased, while H1-T6SS was increased in the PAO1(Δ clpV3 ) strain. We also observed that the intracellular concentration of secondary messenger cAMP was reduced in PAO1(Δ clpV3 ), and the c-di-GMP level was also decreased as indicated by the decreased cdrA reporter activity. Finally, by using a Galleria mellonella infection model, we show that H3-T6SS plays a key role in the pathogenicity of P. aeruginosa in vivo . Overall, our study highlights the unique connection of H3-T6SS in P. aeruginosa with T3SS, pyocyanin production, biofilm formation and in vivo pathogenicity., (Copyright © 2020 Li, Chen, Zhang, Bhagirath and Duan.)

Recently, plant secondary metabolites are considered as important sources of pharmaceuticals, food additives, flavours, cosmetics, and other industrial products. The accumulation of secondary metabolites in plant cell and organ cultures often occurs when cultures are subjected to varied kinds of stresses including elicitors or signal molecules. Application of exogenous jasmonic acid (JA) and methyl jasmonate (MJ) is responsible for the induction of reactive oxygen species (ROS) and subsequent defence mechanisms in cultured cells and organs. It is also responsible for the induction of signal transduction, the expression of many defence genes followed by the accumulation of secondary metabolites. In this review, the application of exogenous MJ elicitation strategies on the induction of defence mechanism and secondary metabolite accumulation in cell and organ cultures is introduced and discussed. The information presented here is useful for efficient large-scale production of plant secondary metabolites by the plant cell and organ cultures. [ABSTRACT FROM AUTHOR]