Rapid kinetics of second messenger production in bitter taste

1996 ◽  
Vol 270 (3) ◽  
pp. C926-C931 ◽  
Author(s):  
A. I. Spielman ◽  
H. Nagai ◽  
G. Sunavala ◽  
M. Dasso ◽  
H. Breer ◽  
...  
Keyword(s):  
Bitter Taste ◽  
Second Messengers ◽  
Second Messenger ◽  
Mouse Strains ◽  
Protective Mechanism ◽  
Transient Nature ◽  
Sucrose Octaacetate ◽  
Rapid Kinetics ◽  
First Time

The tasting of bitter compounds may have evolved as a protective mechanism against ingestion of potentially harmful substances. We have identified second messengers involved in bitter taste and show here for the first time that they are rapid and transient. Using a quench-flow system, we have studied bitter taste signal transduction in a pair of mouse strains that differ in their ability to taste the bitter stimulus sucrose octaacetate (SOA); however, both strains taste the bitter agent denatonium. In both strains of mice, denatonium (10 mM) induced a transient and rapid increase in levels of the second messenger inositol 1,4,5-trisphosphate (IP3) with a maximal production near 75-100 ms after stimulation. In contrast, SOA (100 microM) brought about a similar increase in IP3 only in SOA-taster mice. The response to SOA was potentiated in the presence of GTP (1 microM). The GTP-enhanced SOA-response supports a G protein-mediated response for this bitter compound. The rapid kinetics, transient nature, and specificity of the bitter taste stimulus-induced IP3 formation are consistent with the role of IP3 as a second messenger in the chemoelectrical transduction of bitter taste.

scholarly journals A Survey of Nucleotide Cyclases in Actinobacteria: Unique Domain Organization and Expansion of the Class III Cyclase Family inMycobacterium tuberculosis

2004 ◽  
Vol 5 (1) ◽  
pp. 17-38 ◽  
Author(s):  
Avinash R. Shenoy ◽  
K. Sivakumar ◽  
A. Krupa ◽  
N. Srinivasan ◽  
Sandhya S. Visweswariah
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cyclic Nucleotides ◽  
Metabolic Pathways ◽  
Second Messengers ◽  
Class Iii ◽  
Genome Sequences ◽  
Important Group ◽  
Unique Domain ◽  
First Time

Cyclic nucleotides are well-known second messengers involved in the regulation of important metabolic pathways or virulence factors. There are six different classes of nucleotide cyclases that can accomplish the task of generating cAMP, and four of these are restricted to the prokaryotes. The role of cAMP has been implicated in the virulence and regulation of secondary metabolites in the phylum Actinobacteria, which contains important pathogens, such asMycobacterium tuberculosis, M. leprae, M. bovisandCorynebacterium, and industrial organisms from the genusStreptomyces. We have analysed the actinobacterial genome sequences found in current databases for the presence of different classes of nucleotide cyclases, and find that only class III cyclases are present in these organisms. Importantly, prominent members such asM. tuberculosisandM. lepraehave 17 and 4 class III cyclases, respectively, encoded in their genomes, some of which display interesting domain fusions seen for the first time. In addition, a pseudogene corresponding to a cyclase fromM. aviumhas been identified as the only cyclase pseudogene inM. tuberculosisandM. bovis. TheCorynebacteriumandStreptomycesgenomes encode only a single adenylyl cyclase each, both of which have corresponding orthologues inM. tuberculosis. A clustering of the cyclase domains in Actinobacteria reveals the presence of typical eukaryote-like, fungi-like and other bacteria-like class III cyclase sequences within this phylum, suggesting that these proteins may have significant roles to play in this important group of organisms.

scholarly journals IFN-γ mediated signaling improves fungal clearance in experimental pulmonary mucormycosis.

2021 ◽  
Author(s):  
Amanda Ribeiro dos Santos ◽  
Thais Fernanda Fraga-Silva ◽  
Débora de Fátima Almeida Donanzam ◽  
Rodolfo Ferreira dos Santos ◽  
Angela C. Finato ◽  
...  
Keyword(s):  
Adaptive Immune Response ◽  
Mouse Strains ◽  
Pulmonary Mucormycosis ◽  
Adaptive Immune ◽  
Swiss Mice ◽  
Fungal Load ◽  
Ifn Γ ◽  
First Time ◽  
The Brain

Abstract We established three immunocompetent murine models of pulmonary mucormycosis to determine the involvement of the adaptive immune response in host resistance in pulmonary mucormycosis, a rapidly fatal disease caused mainly by Rhizopus spp. Immunocompetent BALB/c, C57BL/6, and Swiss mice were inoculated with R. oryzae via the intratracheal route. The inoculation resulted in an angioinvasive infection that spread to the brain, spleen, kidney, and liver. After 7 and 30 days of R. oryzae infection, C57BL/6 and BALB/c mice showed the lowest fungal load and highest production of IFN-γ and IL-2 by splenocytes, respectively. Swiss mice showed a higher fungal load 30 days p.i. and was associated with a weak development of the Th-1 profile. To confirm our findings, R. oryzae-infected IFN-γ-/- mice were evaluated after 60 days, where the mice still showed viable fungi in the lungs. This study showed, for the first time, that pulmonary mucormycosis in three widely used mouse strains resulted in an acute fungal dissemination without immunosuppression whose outcome varies according to the genetic background of the mice . We also identified the partial role of IFN-γ in the efficient elimination of R. oryzae during pulmonary infection.

scholarly journals Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused byParacoccidioides brasiliensis

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Laura R. R. Ribeiro ◽  
Flávio V. Loures ◽  
Eliseu F. de Araújo ◽  
Cláudia Feriotti ◽  
Tânia A. Costa ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Pulmonary Infection ◽  
Lipid Mediators ◽  
Mouse Strains ◽  
Cysteinyl Leukotrienes ◽  
Pmn Leukocytes ◽  
Anti Inflammatory ◽  
First Time

Cysteinyl leukotrienes (CysLTs) and lipoxins (LXs) are lipid mediators that control inflammation, with the former inducing and the latter inhibiting this process. Because the role played by these mediators in paracoccidioidomycosis was not investigated, we aimed to characterize the role of CysLT in the pulmonary infection developed by resistant (A/J) and susceptible (B10.A) mice. 48 h after infection, elevated levels of pulmonary LTC4and LXA4were produced by both mouse strains, but higher levels were found in the lungs of susceptible mice. Blocking the CysLTs receptor by MTL reduced fungal loads in B10.A, but not in A/J mice. In susceptible mice, MLT treatment led to reduced influx of PMN leukocytes, increased recruitment of monocytes, predominant synthesis of anti-inflammatory cytokines, and augmented expression of 5- and 15-lipoxygenase mRNA, suggesting a prevalent LXA4activity. In agreement, MTL-treated macrophages showed reduced fungal burdens associated with decreased ingestion of fungal cells. Furthermore, the addition of exogenous LX reduced, and the specific blockade of the LX receptor increased the fungal loads of B10.A macrophages. This study showed for the first time that inhibition of CysLTs signaling results in less severe pulmonary paracoccidioidomycosis that occurs in parallel with elevated LX activity and reduced infection of macrophages.

scholarly journals A revised mechanism for (p)ppGpp synthesis by Rel proteins: The critical role of the 2′-OH of GTP

2020 ◽  
Vol 295 (37) ◽  
pp. 12851-12867
Author(s):  
Pratik Rajendra Patil ◽  
Neha Vithani ◽  
Virender Singh ◽  
Ashok Kumar ◽  
Balaji Prakash
Keyword(s):  
Active Site ◽  
Catalytic Mechanism ◽  
Rna World ◽  
Second Messengers ◽  
Critical Role ◽  
Catalytic Role ◽  
World Hypothesis ◽  
First Time ◽  
Selection Of

Bacterial Rel proteins synthesize hyperphosphorylated guanosine nucleotides, denoted as (p)ppGpp, which by inhibiting energy requiring molecular pathways help bacteria to overcome the depletion of nutrients in its surroundings. (p)ppGpp synthesis by Rel involves transferring a pyrophosphate from ATP to the oxygen of 3′-OH of GTP/GDP. Initially, a conserved glutamate at the active site was believed to generate the nucleophile necessary to accomplish the reaction. Later this role was alluded to a Mg2+ ion. However, no study has unequivocally established a catalytic mechanism for (p)ppGpp synthesis. Here we present a revised mechanism, wherein for the first time we explore a role for 2′-OH of GTP and show how it is important in generating the nucleophile. Through a careful comparison of substrate-bound structures of Rel, we illustrate that the active site does not discriminate GTP from dGTP, for a substrate. Using biochemical studies, we demonstrate that both GTP and dGTP bind to Rel, but only GTP (but not dGTP) can form the product. Reactions performed using GTP analogs substituted with different chemical moieties at the 2′ position suggest a clear role for 2′-OH in catalysis by providing an indispensable hydrogen bond; preliminary computational analysis further supports this view. This study elucidating a catalytic role for 2′-OH of GTP in (p)ppGpp synthesis allows us to propose different mechanistic possibilities by which it generates the nucleophile for the synthesis reaction. This study underscores the selection of ribose nucleotides as second messengers and finds its roots in the old RNA world hypothesis.

Role of Ins(1,4,5)P3, cADP-ribose and nicotinic acid–adenine dinucleotide phosphate in Ca2+ signalling in mouse submandibular acinar cells

2001 ◽  
Vol 353 (3) ◽  
pp. 555-560 ◽  
Author(s):  
Alexander R. HARMER ◽  
David V. GALLACHER ◽  
Peter M. SMITH
Keyword(s):  
Nicotinic Acid ◽  
Second Messengers ◽  
Full Range ◽  
Acinar Cells ◽  
Second Messenger ◽  
Pancreatic Acinar Cells ◽  
Current Response ◽  
Transient Activation ◽  
High Concentrations

cADP-ribose (cADPr) and nicotinic acid–adenine dinucleotide phosphate (NAADP) are two putative second messengers; they were first shown to stimulate Ca2+ mobilization in sea urchin eggs. We have used the patch-clamp whole-cell technique to determine the role of cADPr and NAADP in relation to that of Ins(1,4,5)P3 in mouse submandibular acinar cells by measuring agonist-evoked and second-messenger-evoked changes in Ca2+-dependent K+ and Cl- currents. Both Ins(1,4,5)P3 and cADPr were capable of reproducing the full range of responses normally seen in response to stimulation with acetylcholine (ACh). Low concentrations of agonist (10–20nM ACh) or second messenger [1–10µM Ins(1,4,5)P3 or cADPr] elicited a sporadic transient activation of the Ca2+-dependent currents; mid-range concentrations [50–500nM ACh, 50µM Ins(1,4,5)P3 or 50–100µM cADPr] elicited high-frequency (approx. 2Hz) trains of current spikes; and high concentrations [more than 500nM ACh, more than 50µM Ins(1,4,5)P3 or more than 100µM cADPr] gave rise to a sustained current response. The response to ACh was inhibited by antagonists of both the Ins(1,4,5)P3 receptor [Ins(1,4,5)P3R] and the ryanodine receptor (RyR) but could be completely blocked only by an Ins(1,4,5)P3R antagonist (heparin). NAADP (50nM to 100µM) did not itself activate the Ca2+-dependent ion currents, nor did it inhibit the activation of these currents by ACh. These results show that, in these cells, both Ins(1,4,5)P3R and RyR are involved in the propagation of the Ca2+ signal stimulated by ACh and that cADPr can function as an endogenous regulator of RyR. Furthermore, although NAADP might have a role in hormone-stimulated secretion in pancreatic acinar cells, it does not contribute to ACh-evoked secretion in submandibular acinar cells.

Psychological Resilience Provides No Independent Protection From Suicidal Risk

Crisis ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 130-139 ◽  
Author(s):  
Danica W. Y. Liu ◽  
A. Kate Fairweather-Schmidt ◽  
Richard Burns ◽  
Rachel M. Roberts ◽  
Kaarin J. Anstey
Keyword(s):  
Risk Factors ◽  
Well Being ◽  
Current Status ◽  
Psychological Resilience ◽  
Cross Sectional ◽  
Life Project ◽  
Resilience Factors ◽  
First Time

Abstract. Background: Little is known about the role of resilience in the likelihood of suicidal ideation (SI) over time. Aims: We examined the association between resilience and SI in a young-adult cohort over 4 years. Our objectives were to determine whether resilience was associated with SI at follow-up or, conversely, whether SI was associated with lowered resilience at follow-up. Method: Participants were selected from the Personality and Total Health (PATH) Through Life Project from Canberra and Queanbeyan, Australia, aged 28–32 years at the first time point and 32–36 at the second. Multinomial, linear, and binary regression analyses explored the association between resilience and SI over two time points. Models were adjusted for suicidality risk factors. Results: While unadjusted analyses identified associations between resilience and SI, these effects were fully explained by the inclusion of other suicidality risk factors. Conclusion: Despite strong cross-sectional associations, resilience and SI appear to be unrelated in a longitudinal context, once risk/resilience factors are controlled for. As independent indicators of psychological well-being, suicidality and resilience are essential if current status is to be captured. However, the addition of other factors (e.g., support, mastery) makes this association tenuous. Consequently, resilience per se may not be protective of SI.

Synergetic Theory of Document in Evolution of Document Science

2018 ◽  
pp. 1060-1068
Author(s):  
Galina A. Dvoenosova ◽  
Keyword(s):  
Social Role ◽  
Scientific Study ◽  
Self Organization ◽  
Universal Theory ◽  
Social Self ◽  
Social Goal ◽  
The Social ◽  
Synergetic Theory ◽  
First Time

The article assesses synergetic theory of document as a new development in document science. In information society the social role of document grows, as information involves all members of society in the process of documentation. The transformation of document under the influence of modern information technologies increases its interest to representatives of different sciences. Interdisciplinary nature of document as an object of research leads to an ambiguous interpretation of its nature and social role. The article expresses and contends the author's views on this issue. In her opinion, social role of document is incidental to its being a main social tool regulating the life of civilized society. Thus, the study aims to create a scientific theory of document, explaining its nature and social role as a tool of social (goal-oriented) action and social self-organization. Substantiation of this idea is based on application of synergetics (i.e., universal theory of self-organization) to scientific study of document. In the synergetic paradigm, social and historical development is seen as the change of phases of chaos and order, and document is considered a main tool that regulates social relations. Unlike other theories of document, synergetic theory studies document not as a carrier and means of information transfer, but as a unique social phenomenon and universal social tool. For the first time, the study of document steps out of traditional frameworks of office, archive, and library. The document is placed on the scales with society as a global social system with its functional subsystems of politics, economy, culture, and personality. For the first time, the methods of social sciences and modern sociological theories are applied to scientific study of document. This methodology provided a basis for theoretical vindication of nature and social role of document as a tool of social (goal-oriented) action and social self-organization. The study frames a synergetic theory of document with methodological foundations and basic concepts, synergetic model of document, laws of development and effectiveness of document in the social continuum. At the present stage of development of science, it can be considered the highest form of theoretical knowledge of document and its scientific explanatory theory.

Physical Warmth Attenuates Ethnocentric Bias under Mortality Salience: An Embodied Terror Management Perspective

2020 ◽  
Author(s):  
Armand Chatard ◽  
Margaux Renoux ◽  
Jean Monéger ◽  
Leila Selimbegovic
Keyword(s):  
Mortality Salience ◽  
Terror Management ◽  
Negative Consequences ◽  
Defensive Reaction ◽  
Worldview Defense ◽  
Management Perspective ◽  
Physical Warmth ◽  
Alternative Means ◽  
First Time

Research indicates that individuals often deal with mortality salience by affirming beliefs in national or cultural superiority (worldview defense). Because worldview defense may be associated with negative consequences (discrimination), it is important to identify alternative means to deal with death-related thoughts. In line with an embodied terror management perspective, we evaluate for the first time the role of physical warmth in reducing defensive reaction to mortality salience. We predicted that, like social affiliation (social warmth), physical warmth could reduce worldview defense when mortality is salient. In this exploratory (preregistered) study, 202 French participants were primed with death-related thoughts, or an aversive control topic, in a heated room or a non-heated room. The main outcome was worldview defense (ethnocentric bias). We found no main effect of mortality salience on worldview defense. However, physical warmth reduced worldview defense when mortality was salient. Implications for an embodied terror management perspective are discussed.

Relationship between big five personality model and abusive supervision

2019 ◽  
Vol 12 (2) ◽  
Author(s):  
Bibi Tahira ◽  
Naveed Saif ◽  
Muhammad Haroon ◽  
Sadaqat Ali
Keyword(s):  
Big Five ◽  
Abusive Supervision ◽  
State Universities ◽  
Big Five Personality ◽  
Big Five Model ◽  
The Impact ◽  
First Time ◽  
Supervisor Behavior ◽  
Moderating Role

The current study tries to understand the diverse nature of relationship between personality Big Five Model (PBFM) and student's perception of abusive supervision in higher education institutions of Khyber Pakhtoonkhwa Pakistan. Data was collected in dyads i.e. (supervisors were asked to rate their personality attributes while student were asked to rate the supervisor behavior) through adopted construct. For this purpose, data was collected from three government state universities and one Private Sector University. The focus was on MS/M.Phill and PhD student and their supervisors of the mentioned universities. After measuring normality and validity regression analysis was conducted to assess the impact of supervisor personality characteristics that leads to abusive supervision. Findings indicate interestingly that except agreeableness other four attributes of (PBFM) are play their role for abusive supervision. The results are novel in the nature as for the first time Neuroticism, openness to experience, extraversion and conscientiousness are held responsible for the abusive supervision. The study did not explore the demographic characteristics, and moderating role of organizational culture, justice and interpersonal deviances to understand the strength of relationship in more detail way. Keywords: Personality big five model, abusive supervision, HEIs

Smolensk Proper Names in A.T. Tvardovsky’s Poems

2020 ◽  
pp. 54-62
Author(s):  
Inna A. Koroleva ◽  
Keyword(s):  
Proper Names ◽  
Personal Characteristics ◽  
Entire Body ◽  
Literary Works ◽  
Thematic Content ◽  
Home Town ◽  
Birthday Anniversary ◽  
Long Poems ◽  
First Time

This article is dedicated to the 110th birthday anniversary of a great Russian poet, native of Smolensk, one of the founders of the Smolensk Poetic School Aleksandr Tvardovsky (1910–1971). It examines how Smolensk motifs and Tvardovsky’s love for his home town are reflected in his works at the onomastic level. Smolensk-onyms reflected in long poems are analysed here, the focus being on anthroponyms and toponyms naming the characters and indicating the locations associated with Smolensk region. A close connection between the choice of proper names and Tvardovsky’s biography is established. An attempt is made to demonstrate how, using onomastic units introduced by the author into the storyline of his artistic text, the general principles of autobiography and chronotopy are realized, which have been noted earlier in critiques of Tvardovsky’s literary works. The onomastic component of the poems is analysed thoroughly and comprehensively, which helps us to decode the conceptual chain writer – name – text – reader and identify the author’s attitude to the characters and the ideological and thematic content of the works, as well as some of the author’s personal characteristics, tastes and passions. At the onomastic level, the thesis about the role of Smolensk motifs in Tvardovsky’s literary works is once more substantiated. A review is presented of onomastic studies analysing proper names of different categories in Tvardovsky’s poems (mainly conducted by the representatives of the Voronezh Onomastic School and the author of this article). It should be noted that Smolensk proper names in the entire body of Tvardovsky’s poetry are analysed for the first time.

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