Cloning, Sequencing, and Functional Analysis of the Biosynthetic Gene Cluster of Macrolactam Antibiotic Vicenistatin in Streptomyces halstedii

AbstractVicenistatin, an antitumor antibiotic isolated from Streptomyces halstedii, is a unique 20-membered macrocyclic lactam with a novel aminosugar vicenisamine. The vicenistatin biosynthetic gene cluster (vin) spanning ∼64 kbp was cloned and sequenced. The cluster contains putative genes for the aglycon biosynthesis including four modular polyketide synthases (PKSs), glutamate mutase, acyl CoA-ligase, and AMP-ligase. Also found in the cluster are genes of NDP-hexose 4,6-dehydratase and aminotransferase for vicenisamine biosynthesis. For the functional confirmation of the cluster, a putative glycosyltransferase gene product, VinC, was heterologously expressed, and the vicenisamine transfer reaction to the aglycon was chemically proved. A unique feature of the vicenistatin PKS is that the loading module contains only an acyl carrier protein domain, in contrast to other known PKS-loading modules containing certain activation domains. Activation of the starter acyl group by separate polypeptides is postulated as well

Notes on S-Matrix of Non-critical N=2 String

In this paper we discuss the scattering S-matrix of non-critical N=2 string at tree level. First we consider the \hat{c}<1 string defined by combining the N=2 time-like linear dilaton SCFT with the N=2 Liouville theory. We compute three particle scattering amplitudes explicitly and find that they are actually vanishing. We also find an evidence that this is true for higher amplitudes. Next we analyze another \hat{c}<1 string obtained from the N=2 time-like Liouville theory, which is closely related to the N=2 minimal string. In this case, we find a non-trivial expression for the three point functions. When we consider only chiral primaries, the amplitudes are very similar to those in the (1,n) non-critical bosonic string.Comment: 27 pages, harvmac, section 5 modified: a relation to (1,n) non-critical bosonic string adde

c < 1 String from Two Dimensional Black Holes

We study a topological string description of the c < 1 non-critical string whose matter part is defined by the time-like linear dilaton CFT. We show that the topologically twisted N=2 SL(2,R)/U(1) model (or supersymmetric 2D black hole) is equivalent to the c < 1 non-critical string compactified at a specific radius by comparing their physical spectra and correlation functions. We examine another equivalent description in the topological Landau-Ginzburg model and check that it reproduces the same scattering amplitudes. We also discuss its matrix model dual description.Comment: 36 pages, harvmac; acknowledgements, comments and references adde

Comments on 2D Type IIA String and Matrix Model

We consider a type IIA-like string theory with RR-flux in two dimension and propose its matrix model dual. This string theory describes a Majorana fermion in the two dimensional spacetime. We also discuss its scattering amplitudes both in the world-sheet theory and in the matrix model.Comment: 21 pages, Harvmac, to appear in JHEP, relation to 2d superstring constructed by D. Kutasov hep-th/9110041 is clarifie

On the Connection between N=2 Minimal String and (1,n) Bosonic Minimal String

We study the scattering amplitudes in the N=2 minimal string or equivalently in the N=4 topological string on ALE spaces. We find an interesting connection between the tree level amplitudes of the N=2 minimal string and those of the (1,n) minimal bosonic string. In particular we show that the four and five-point functions of the N=2 string can be directly rewritten in terms of those of the latter theory. This relation offers a map of physical states between these two string theories. Finally we propose a possible matrix model dual for the N=2 minimal string in the light of this connection.Comment: 40 pages, one figure, harvmac, minor corrections, references adde

Holomorphic Tachyons and Fractional D-branes

We study tachyon condensation on brane-antibrane systems in orbifold theories from the viewpoint of boundary string field theory. We show that the condensation of holomorphic tachyon fields generates various fractional D-branes. The boundary N=2 supersymmetry in the world-sheet theory ensures this result exactly. Furthermore, our results are consistent with the twisted RR-charges from detailed calculations of boundary states. We also discuss the generation of RR-charges due to holomorphic tachyon fields on multiple brane-antibrane pairs in flat space.Comment: Latex, 30 pages, v2:typos corrected and references added, v3:comments and references adde

Notes on D-branes in 2D Type 0 String Theory

In this paper we construct complete macroscopic operators in two dimensional type 0 string theory. They represent D-branes localized in the time direction. We give another equivalent description of them as deformed Fermi surfaces. We also discuss a continuous array of such D-branes and show that it can be described by a matrix model with a deformed potential. For appropriate values of parameters, we find that it has an additional new sector hidden inside its strongly coupled region.Comment: harvmac, 18 pages, 2 figures, references adde

Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions

The 18F-labeled fibroblast activation protein inhibitor (FAPI) [18F]FAPI- 74 has the benefit of a higher synthetic yield and better image resolution than 68Ga-labeled FAPI. We preliminarily evaluated the diagnostic performance of [18F]FAPI-74 PET in patients with various histopathologically confirmed cancers or suspected malignancies. Methods: We enrolled 31 patients (17 men and 14 women) with lung cancer (n = 7), breast cancer (n = 5), gastric cancer (n = 5), pancreatic cancer (n = 3), other cancers (n = 5), and benign tumors (n = 6). Twenty-seven of the 31 patients were treatment-naïve or preoperative, whereas recurrence was suspected in the remaining 4 patients. Histopathologic confirmation was obtained for the primary lesions of 29 of the 31 patients. In the remaining 2 patients, the final diagnosis was based on the clinical course. [18F]FAPI-74 PET scanning was performed 60min after the intravenous injection of [18F]FAPI-74 (240631 MBq). The [18F]FAPI-74 PET images were compared between the primary or local recurrent lesions of malignant tumors (n = 21) and nonmalignant lesions (n 5 8: type-B1 thymomas, granuloma, solitary fibrous tumor, and postoperative or posttherapeutic changes). The uptake and number of detected lesions on [18F]FAPI-74 PET were also compared with those on [18F]FDG PET for available patients (n = 19). Results: [18F]FAPI-74 PET showed higher uptake in primary lesions of various cancers than in nonmalignant lesions (median SUVmax, 9.39 [range, 1.83-25.28] vs. 3.49 [range, 2.21-15.58]; P = 0.053), but some of the nonmalignant lesions showed high uptake. [18F]FAPI-74 PET also showed significantly higher uptake than [18F]FDG PET (median SUVmax, 9.44 [range, 2.50-25.28] vs. 5.45 [range, 1.22-15.06] in primary lesions [P 5 0.010], 8.86 [range, 3.51-23.33] vs. 3.84 [range, 1.01-9.75] in lymph node metastases [P 5 0.002], and 6.39 [range, 0.55-12.78] vs. 1.88 [range, 0.73-8.35] in other metastases [P 5 0.046], respectively). In 6 patients, [18F]FAPI-74 PET detected more metastatic lesions than [18F]FDG PET. Conclusion: [18F]FAPI-74 PET showed higher uptake and detection rates in primary and metastatic lesions than did [18F]FDG PET. [18F]FAPI-74 PET is a promising novel diagnostic modality for various tumors, especially for precise staging before treatment, including characterization of tumor lesions before surgery. Moreover, 18F-labeled FAPI ligand might serve a higher demand in clinical care in the future.This research was originally published in JNM. Tadashi Watabe, Sadahiro Naka, Mitsuaki Tatsumi et.al. Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions. J Nucl Med. 2023, 64(8), 1225-1231. © SNMMI

Flux Backgrounds in 2D String Theory

We study RR flux backgrounds in two dimensional type 0 string theories. In particular, we study the relation between the 0A matrix model and the extremal black hole in two dimensions. Using T-duality we find a dual flux background in type 0B theory and propose its matrix model description. When the Fermi level is set to zero this system remains weakly coupled and exhibits a larger symmetry related to the structure of flux vacua. Finally, we construct a two dimensional type IIB background as an orbifold of the 0B background.Comment: Harvmac, 40 pages, 6 figs, minor changes, references adde

Angiotensin receptors in GtoPdb v.2023.1

The actions of angiotensin II (Ang II) are mediated by AT1 and AT2 receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Angiotensin receptors [63, 155]), which have around 30% sequence similarity. The decapeptide angiotensin I, the octapeptide angiotensin II and the heptapeptide angiotensin III are endogenous ligands. losartan, candesartan, olmesartan, telmisartan, etc. are clinically used AT1 receptor blockers