scholarly journals The Molecular Mechanism of Fludioxonil Action Is Different to Osmotic Stress Sensing

2021 ◽  
Vol 7 (5) ◽  
pp. 393
Author(s):  
Katharina Bersching ◽  
Stefan Jacob

The group III two-component hybrid histidine kinase MoHik1p in the filamentous fungus Magnaporthe oryzae is known to be a sensor for external osmotic stress and essential for the fungicidal activity of the phenylpyrrole fludioxonil. The mode of action of fludioxonil has not yet been completely clarified but rather assumed to hyperactivate the high osmolarity glycerol (HOG) signaling pathway. To date, not much is known about the detailed molecular mechanism of how osmotic stress is detected or fungicidal activity is initiated within the HOG pathway. The molecular mechanism of signaling was studied using a mutant strain in which the HisKA signaling domain was modified by an amino acid change of histidine H736 to alanine A736. We found that MoHik1pH736A is as resistant to fludioxonil but not as sensitive to osmotic stress as the null mutant ∆Mohik1. H736 is required for fludioxonil action but is not essential for sensing sorbitol stress. Consequently, this report provides evidence of the difference in the molecular mechanism of fludioxonil action and the perception of osmotic stress. This is an excellent basis to understand the successful phenylpyrrole-fungicides’ mode of action better and will give new ideas to decipher cellular signaling mechanisms.

Author(s):  
Katharina Bersching ◽  
Stefan Jacob

The group III two-component hybrid histidine kinase MoHik1p in the filamentous fungus Magnaporthe oryzae is known to be a sensor for external osmotic stress and essential for the fungicidal activity of the phenylpyrrole fludioxonil. The mode of action of fludioxonil has not yet been completely clarified but rather assumed to hyperactivate the high osmolarity glycerol (HOG) signaling pathway. To date, not much is known about the detailed molecular mechanism of how osmotic stress is detected or fungicidal activity is initiated within the HOG pathway. The molecular mechanism of signaling was studied using a mutant strain in which the HisKA signaling domain was modified by an amino acid change of histidine H736 to alanine A736. We found that MoHik1pH736A is as resistant to fludioxonil but not as sensitive to osmotic stress as the null mutant ∆Mohik1. H736 is required for fludioxonil action but is not essential for sensing sorbitol stress. Consequently, this report provides evidence of the difference in the molecular mechanism of fludioxonil action and the perception of osmotic stress. This is an excellent basis to understand the successful phenylpyrrole-fungicides’ mode of action better and will give new ideas to decipher cellular signaling mechanisms.


2007 ◽  
Vol 51 (10) ◽  
pp. 3734-3736 ◽  
Author(s):  
Leandro Vetcher ◽  
Hugo G. Menzella ◽  
Toshiaki Kudo ◽  
Takayuki Motoyama ◽  
Leonard Katz

ABSTRACT The polyketide ambruticin is an attractive candidate for drug development as an antifungal agent, but its mechanism of action has not yet been elucidated. Here we present evidence that ambruticin exerts its effect by targeting HOG, the osmotic stress control pathway, through Hik1, a group III histidine kinase.


1991 ◽  
Vol 260 (3) ◽  
pp. H730-H734 ◽  
Author(s):  
P. N. McWilliam ◽  
T. Yang

The action of electrically evoked activity in somatic afferent fibers on the sensitivity of the baroreceptor reflex was examined in decerebrate cats. The sensitivity of the reflex was expressed as the difference between the maximum prolongation of R-R interval in response to carotid sinus pressure elevation and the mean of 10 R-R intervals immediately before pressure elevation. The control value of R-R interval prolongation was 192 +/- 50 ms. Stimulation (10 Hz) of group I and II fibers of the right peroneal nerve (evoked volleys recorded from the sciatic nerve) had no effect on R-R interval prolongation (171 +/- 45 ms). Recruitment of group III fibers (10 Hz) conducting at 23.6 +/- 0.65 m/s reduced the prolongation of R-R interval to 52 +/- 14 ms. Recruitment of group IV fibers (10 Hz) conducting less than 2.5 m/s further reduced the prolongation of R-R interval to 1.0 +/- 8.0 ms. It is concluded that the inhibition of the cardiac vagal component of the baroreceptor reflex produced by electrical stimulation of the peroneal nerve is mediated by afferent fibers of groups III and IV.


1960 ◽  
Vol 11 (1) ◽  
pp. 75 ◽  
Author(s):  
M Wodzicka

The monthly wool growth of three groups of rams was studied at Beltsville, Maryland. Group I received natural daylight (at 38° 53' N.) and was shorn monthly. Group II had a 7:17 hours of daylight to hours of darkness rhythm and was shorn every 6 months, once in winter and once in summer. Group III received natural daylight and was likewise shorn every 6 months. The rams of all groups produced more wool in summer than in winter. This difference was significant (P<0.001). The mean body weight and food intake were both greater in the winter months, which indicated that the seasonal rhythm of wool growth was not a consequence of poorer feeding in winter. The rams which were shorn monthly (group I) grew considerably more wool than the other two groups, but the difference was not statistically significant. The short-day treatment of group II did not increase the annual wool production nor decrease the seasonal rhythm of wool growth. The balance of evidence from this and other experiments indicates that temperature rather than light controls the seasonal rhythm of wool growth.


2005 ◽  
Vol 93 (01) ◽  
pp. 76-79 ◽  
Author(s):  
Alain Leizorovicz ◽  
Alexander Cohen ◽  
Alexander Turpie ◽  
Carl-Gustav Olsson ◽  
Samuel Goldhaber ◽  
...  

SummaryThe clinical importance of asymptomatic proximal and distal deep vein thrombosis (DVT) remains uncertain and controversial. The aim of this retrospective,post-hoc analysis was to examine mortality and risk factors for development of proximal DVT in hospitalized patients with acute medical illness who were recruited into a randomized, prospective clinical trial of thromboprophylaxis with dalteparin (PREVENT).We analyzed 1738 patients who had not sustained a symptomatic venous thromboembolic event by Day 21 and who had a complete compression ultrasound of the proximal and distal leg veins on Day 21. We examined the 90-day mortality rates in patients with asymptomatic proximal DVT (Group I, N = 80), asymptomatic distal DVT (Group II, N = 118) or no DVT (Group III, N = 1540).The 90-day mortality rates were 13.75%, 3.39%, and 1.92% for Groups I–III, respectively. The difference in mortality between Group I and Group III was significant (hazard ratio 7.63, 95% CI = 3.8–15.3;p < 0.0001),whereas the difference between Groups II and III did not reach significance (hazard ratio 1.36, 95% CI = 0.41–4.45).The association of asymptomatic proximal DVT with increased mortality remained highly significant after adjusting for differences in baseline demographics and clinical variables. Risk factors significantly associated with the development of proximal DVT included advanced age (p = 0.0005), prior DVT (p = 0.001), and varicose veins (p = 0.04). In conclusion, the high mortality rate in patients with asymptomatic proximal DVT underscores its clinical relevance and supports targeting of asymptomatic proximal DVT as an appropriate endpoint in clinical trials of thromboprophylaxis.


1987 ◽  
Vol 62 (3) ◽  
pp. 946-951 ◽  
Author(s):  
D. F. Speck ◽  
W. R. Revelette

The projections of phrenic nerve afferents to neurons in the dorsal (DRG) and ventral (VRG) respiratory group were studied in anesthetized, paralyzed, and vagotomized cats. Extracellular recordings of neuronal responses to vagal nerve and cervical phrenic nerve stimulation (CPNS) indicated that about one-fourth of the DRG respiratory-modulated neurons were excited by phrenic nerve afferents with an onset latency of approximately 20 ms. In addition, non-respiratory-modulated neurons within the DRG were recruited by CPNS. Although some convergence of vagal and phrenic afferent input was observed, most neurons were affected by only one type of afferent. In contrast to the DRG, only 3 out of 28 VRG respiratory-modulated neurons responded to CPNS. A second study determined that most of these neuronal responses were due to activation of diaphragmatic afferents since 90% of the DRG units activated by CPNS were also excited at a longer latency by thoracic phrenic nerve stimulation. The difference in onset latency of neuronal excitation indicates an afferent peripheral conduction velocity of about 10 m/s, which suggests that they are predominately small myelinated fibers (group III) making paucisynaptic connections with DRG neurons. Decerebration, decerebellation, and bilateral transection of the dorsal columns at C2 do not abolish the neuronal responses to cervical PNS.


1994 ◽  
Vol 14 (6) ◽  
pp. 4135-4144
Author(s):  
J Albertyn ◽  
S Hohmann ◽  
J M Thevelein ◽  
B A Prior

The yeast Saccharomyces cerevisiae responds to osmotic stress, i.e., an increase in osmolarity of the growth medium, by enhanced production and intracellular accumulation of glycerol as a compatible solute. We have cloned a gene encoding the key enzyme of glycerol synthesis, the NADH-dependent cytosolic glycerol-3-phosphate dehydrogenase, and we named it GPD1. gpd1 delta mutants produced very little glycerol, and they were sensitive to osmotic stress. Thus, glycerol production is indeed essential for the growth of yeast cells during reduced water availability. hog1 delta mutants lacking a protein kinase involved in osmostress-induced signal transduction (the high-osmolarity glycerol response [HOG] pathway) failed to increase glycerol-3-phosphate dehydrogenase activity and mRNA levels when osmotic stress was imposed. Thus, expression of GPD1 is regulated through the HOG pathway. However, there may be Hog1-independent mechanisms mediating osmostress-induced glycerol accumulation, since a hog1 delta strain could still enhance its glycerol content, although less than the wild type. hog1 delta mutants are more sensitive to osmotic stress than isogenic gpd1 delta strains, and gpd1 delta hog1 delta double mutants are even more sensitive than either single mutant. Thus, the HOG pathway most probably has additional targets in the mechanism of adaptation to hypertonic medium.


Karl Barth ◽  
2021 ◽  
pp. 84-99
Author(s):  
Christiane Tietz

The support of prominent theologians for the First World War made Barth understand that their premises were false. How instead could a pastor rightly speak of God? Barth returned anew to the biblical text, becoming convinced that it can still speak to people today. The result was Barth’s first Epistle to the Romans (1919), a commentary to Paul’s letter. Barth stresses that the kingdom of God comes about solely through God, while all human activities, including religion, belong to the world. Barth’s cultural critique reflects the spiritual situation of the wartime and postwar period, yet without any hope on cultural renewal. In his 1919 Tambach lecture, Barth further developed his insights of the difference between God and religion. For God one can only wait. Jesus Christ’s resurrection is the wholly other. Therefore theology needs to think dialectically. Barth’s new ideas found great resonance, but he was also accused of arbitrary exegesis.


2019 ◽  
pp. 359-365
Author(s):  
Tetiana Tsymbaliuk-Skopnenko

The term divergence is used traditionally in linguistics in origin of language and dialectology to denote the distinction between certain idioms. However, the unit under consideration was used in a wider context, because it denotes the process and the consequence that are caused by the distinction of features and properties of objects – something that ultimately leads to the division of the previously indistinguishable, and hence the appearance of new ideas about the world. In word formation, divergence is understood as the differentiation of common-root derivatives in terms of content or peculiarities of their use. Researchers also use the notions of semantic divergence – the difference in the content structure of derivative units with certain semantic nuances, which shows their semantic non-identity. Phraseography – conventionally derivative unit of lexemy lexicography, in this case we must talk about creating the first term by model of the second. For a long time in the scientific literature lexicography was used to refer to the section of linguistics, within which, with the help of certain methods, both lexemes and phraseologisms are described, although these units have different nature. The growth of phraseology as a separate scientific field did not automatically lead to the fixing of the term phrazeography in the national scientific discourse. Modern search engines on the Internet provide information that in this network found over a thousand documents in the Ukrainian language, which includes the word phrazeography. Certainly, this cannot be an example of the frequency of the use of this lexeme, but this fact suggests that in the modern scientific world there is a critical mass for understanding of the phrazeography as a separate scientific field. Some important arguments against this tendency were not found, although in modern university textbook phrazeography information is presented in the section “Phraseology” or at the end of “Lexicsology”, while lexicography as a separate branch, not within the limits of lexicology, has long been entrenched in the educational and scientific literature. And it sounds paradoxical to a certain extent, because it is from phraseology (however, in symbiosis with lexicography), not only the newest Ukrainian phraseology as a science began, the description of phraseological units was one of the first tasks of Ukrainian vocabulary in general. In addition, we note that the term “science about dictionaries” is most often used in the sense of “lexicography”. Since the tradition of non-differentiation of lexicography and phraseology is very strong, it would be expedient (and simply convenient) to use this Ukrainian term for the definition of synthetic understanding of the two branches of philology as a related unity: lexicography (theoretical and practical) and phrazeography (also theoretical and practical). If we accept such a proposal, then there will be no unnecessary confrontation between lexicography and phrazeography, the uncertainty of which leads to many misunderstandings. We can conclude that there is no reason to denote by the term lexicography the whole set of scientific approaches related to the phrazeography description. In Ukrainian linguistics, it is necessary to clearly delineate the terms lexicography and phrazeography, since they, over the last time, consolidated various semantic concepts.


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