Although the A1 adenosine receptor (A1 receptor), the main adenosine receptor type in cardiac muscle, is involved in powerful cardioprotective processes such as ischemic preconditioning, the atrial A1 receptor reserve has not yet been quantified for the direct negative inotropic effect of adenosine. In the present study, adenosine concentration-effect (E/c) curves were constructed before and after pretreatment with FSCPX (8-cyclopentyl-N3-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-N1-propylxanthine), an irreversible A1 receptor antagonist, in isolated guinea pig atria. To prevent the intracellular elimination of the administered adenosine, NBTI (S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine), a nucleoside transport inhibitor, was used. As expected, NBTI alone and FSCPX-pretreatment alone shifted the adenosine E/c curve to the left and right, respectively. However, in the presence of NBTI, FSCPX-pretreatment appeared to increase the maximal response to adenosine. By means of the receptorial responsiveness method (RRM), our recently developed procedure, adenosine E/c curves generated in the presence of NBTI were corrected for the bias caused by the endogenous adenosine accumulated by NBTI. The corrected curves indicate a substantial A1 receptor reserve for the direct negative inotropy evoked by adenosine. In addition, our results suggest that accumulation of an endogenous agonist may bias the E/c curve constructed with the same or similar agonist that can lead to seemingly paradoxical results.
A1 adenosine receptors (A1 receptors) are widely expressed in mammalian tissues; therefore attaining proper tissue selectivity is a cornerstone of drug development. The fact that partial agonists chiefly act on tissues with great receptor reserve can be exploited to achieve an appropriate degree of tissue selectivity. To the best of our knowledge, the A1 receptor reserve has not been yet quantified for the atrial contractility. A1 receptor reserve was determined for the direct negative inotropic effect of three A1 receptor full agonists (NECA, CPA and CHA) in isolated, paced guinea pig left atria, with the use of FSCPX, an irreversible A1 receptor antagonist. FSCPX caused an apparently pure dextral displacement of the concentration-response curves of A1 receptor agonists. Accordingly, the atrial A1 receptor function converging to inotropy showed a considerably great, approximately 80-92 % of receptor reserve for a near maximal (about 91-96 %) effect, which is greater than historical atrial A1 receptor reserve data for any effects other than inotropy. Consequently, the guinea pig atrial contractility is very sensitive to A1 receptor stimulation. Thus, it is worthwhile considering that even partial A1 receptor agonists, given in any indication, might decrease the atrial contractile force, as an undesirable side effect, in humans.
Streptomyces griseus strain 45H, isolated in 1960 during a mutagenesis programme on the industrial streptomycin producer S. griseus 52-1, encodes an extracellular, pleiotropic autoregulatory signalling protein, factor C, which stimulates sporulation of S. griseus 52-1 in submerged culture. The facC gene, which codes for factor C, is present in very few streptomycetes and is not present in S. griseus 52-1. Based on 16S rRNA gene sequencing and other molecular data, S. griseus 45H, the factor C producer, is here shown to be related to the original laboratory strain of Streptomyces flavofungini, which was being studied in the same laboratory in 1960, and to Streptomyces albidoflavus. Southern blotting revealed that three out of four independently isolated strains of S. albidoflavus possess facC. Both the original strain of S. flavofungini and S. griseus 45H are therefore identified as members of the species Streptomyces albidoflavus, and we propose that S. griseus 45H should be renamed Streptomyces albidoflavus 45H.It has been known for a long time that antibiotic production is restricted to a specific short period of the complex developmental cycle of the producer streptomycetes and that the regulation of antibiotic production is intimately interconnected with morphogenesis (Chater, 1998). This connection underlines the continuing interest in studying the morphological differentiation of many Streptomyces strains.Streptomyces griseus 45H was isolated during a mutagenesis programme aimed at the isolation of morphological mutants (non-sporulating and hypersporulating) of the industrial streptomycin producer strain Streptomyces griseus 52-1 (Szabó et al., 1960(Szabó et al., , 1961. S. griseus 45H has been described as a strain that sporulates well both on solid medium and in liquid culture, the latter being a rather rare property of Streptomyces strains. In addition, the strain secreted a substance, named factor C, into the culture medium that also induced cytodifferentiation of S. griseus 52-1 and stimulated sporulation in liquid culture.The activity of factor C was shown to be due to a protein (Biró et al., 1980). The cloning and sequencing of the facC gene (Birkó et al., 1999), which encodes this extracellular signalling protein, revealed a gene with no close relatives in the database at that time. The identity and mode of action of factor C, the morphological differentiation of S. griseus 45H and the effect of factor C on the differentiation of S. griseus 52-1 have been the subject of many publications (for a complete list see http://web.dote.hu/~sbiro/). Interaction between factor C and the regulon of S. griseus controlled by the best known c-butyrolactone autoregulator, A-factor (Ohnishi et al., 2005), has been described recently (Birkó et al., 2007).Since the two S. griseus strains (52-1 and 45H) differed in several substantial properties (Table 1), the origin of S. griseus 45H has often been questioned (Fehér & Szabó , 1978). Unquestionable evidence that the strain S. griseus 45H could not be a descendant of...
In eukaryotes the TFIID complex is required for preinitiation complex assembly which positions RNA polymerase II around transcription start sites. On the other hand, histone acetyltransferase complexes including SAGA and ATAC, modulate transcription at several steps through modification of specific core histone residues. In this study we investigated the function of Drosophila melanogaster proteins TAF10 and TAF10b, which are subunits of dTFIID and dSAGA, respectively. We generated a mutation which eliminated the production of both Drosophila TAF10 orthologues. The simultaneous deletion of both dTaf10 genes impaired the recruitment of the dTFIID subunit dTAF5 to polytene chromosomes, while binding of other TFIID subunits, dTAF1 and RNAPII was not affected. The lack of both dTAF10 proteins resulted in failures in the larval-pupal transition during metamorphosis and in transcriptional reprogramming at this developmental stage. Surprisingly, unlike dSAGA mutations, dATAC subunit mutations resulted in very similar changes in the steady state mRNA levels of approximately 5000 genes as did ablation of both dTaf10 genes, indicating that dTAF10- and/or dTAF10b-containing complexes and dATAC affect similar pathways. Importantly, the phenotype resulting from dTaf10+dTaf10b mutation could be rescued by ectopically added ecdysone, suggesting that dTAF10- and/or dTAF10b-containing complexes are involved in the expression of ecdysone biosynthetic genes. Indeed, in dTaf10+dTaf10b mutants, cytochrome genes, which regulate ecdysone synthesis in the ring gland, were underrepresented. Therefore our data support the idea that the presence of dTAF10 proteins in dTFIID and/or dSAGA is required only at specific developmental steps. We propose that distinct forms of dTFIID and/or dSAGA exist during Drosophila metamorphosis, wherein different TAF compositions serve to target RNAPII at different developmental stages and tissues.
Összefoglaló. Bevezetés: A hímtag körméretének növelése érdekében, az annak bőre alá bejuttatott zsírnemű anyag szklerotizáló lipogranulomát okoz. Hazánkban a szklerotizáló lipogranuloma okozta hímvessző-deformitások kezelésének legelterjedtebb módszere a két ülésben végzett bőrpótlás. Ennek ellenére a magyar nyelvű szakirodalomban kevés adat áll rendelkezésre a kétüléses műtét eredményességéről és várható szövődményeiről. Célkitűzés: Tanulmányunkban a szklerotizáló lipogranuloma okozta deformitások miatti – két ülésben végzett – hímvesszőbőr-helyreállítással szerzett tapasztalatainkról, a műtét után kialakuló szövődményekről számolunk be retrospektív adatgyűjtés alapján. Módszer: 2008. március 1. és 2020. március 1. között a Debreceni Egyetem Urológiai Klinikáján 17 betegen végeztünk kétüléses hímvesszőbőr-helyreállító műtétet. A szklerotizáló lipogranuloma által érintett bőrt teljes mértékben eltávolítottuk, majd a lecsupaszított hímtagot a herezacskó elülső felszínén kialakított subcutan csatornába helyeztük. A második ülés során a herezacskó bőre alá ültetett hímvesszőt felszabadítottuk. Eredmények: A Clavien–Dindo-beosztás szerint az első ülés után három, a második ülés után egy I. gradusú szövődmény alakult ki; II–V. gradusú szövődményt nem figyeltünk meg. Azon 9 beteg közül, akik mindkét ülésen átestek, 7 beteg elégedett volt a beavatkozás eredményével, 2 beteg korrekciós műtéten esett át fél és 9 évvel a második ülés után. A 8 beteg közül, akik csak ez első ülést vállalták, egy korrekciós műtét történt 4 hónappal a műtét után. Következtetés: A hímvessző szklerotizáló lipogranulomája esetén az érintett bőrterület kimetszése után hímvesszőbőr-helyreállítás szükséges. A herezacskó-bőrlebeny alkalmazásának előnye, hogy a herezacskó színe és elaszticitása a hímvesszőbőréhez hasonló, a tapintás- és erogén érzet megmarad. A kétüléses hímvesszőbőr-helyreállítás kevés szövődménnyel, plasztikai sebészeti jártasság nélkül elvégezhető. Orv Hetil. 2021; 162(35): 1413–1417. Summary. Introduction: Subcutaneous injection of liquid fatty materials to enhance penile girth induce sclerosing lipogranuloma of the penis. In spite of its well known severe consequences there has been a persistent use of this practice in non-medical circumstances. Objective: The aim of this paper is to present our observations with staged penile skin reconstruction for sclerosing lipogranuloma and to evaluate postoperative complications in a retrospective manner. Method: Between 2008 and 2020, 17 patients underwent surgery to treat sclerosing lipogranuloma of the penis by staged penile skin reconstruction at our department. Complete exscision of the involved tissue was performed, then the denuded penile shaft was inserted into a subcutaneous channel on the anterior side of the scrotum during the first stage. The second stage of reconstruction consisted of releasing the penile shaft from the scrotum. The second stage was performed merely on 9 in 17 patients. Results: According to the Clavien–Dindo classification system, 3 grade I and 1 grade I complications occurred in the postoperative period after the first and second stage, respectively. Grade II–V complications were not observed. 7 of 9 patients who underwent both stages were satisfied with the final result, 2 patients had minor correction surgery 6 months and 9 years following the second stage. 1 of 8 patients who underwent only the first stage had minor correction surgery 4 months following the operation. Conclusion: In case of sclerosing lipogranuloma of the penis, excision of the affected tissue and reconstruction of the penile skin are indicated. Advantages of using scrotal skin flaps are that colour and elasticity of the scrotal skin are similar to penile skin, erogenous sensation of the scrotal flap remains intact. Applying staged penile skin reconstruction with scrotal skin flap has the advantage of few postoperative complications and it is easy to perform. Orv Hetil. 2021; 162(35): 1413–1417.
Switchgrass ( Panicum virgatum L.) biomass, which is of a good quality in the middle of summer, when cool-season grasses are unproductive, is a very important source of forage. This study measured the influence of the date of first harvest and cutting height on the first and regrowth yields of switchgrass cultivars Blackwell and Cave in Rock. The experiment was conducted in Blacksburg, VA, USA on a Groseclose-Poplimento soil to determine the influence of four dates of harvest and two cutting heights on the yield of switchgrass in 1990, and the influence of the treatments in previous years on the yields in 1991 and 1992. The first yield of both cultivars increased as the date of first harvest was delayed and the cutting height reduced. The regrowth yield of both cultivars declined as the date of first harvest was delayed. A shorter cutting height caused reductions in vigour and yield potential in the second year, whilst in the third year the harvested yield was only 40–50% of that obtained from previously unharvested stands.
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