Página 3 dos resultados de 4272 itens digitais encontrados em 0.037 segundos

A Burkholderia cepacia complex non-ribosomal peptide-synthesized toxin is hemolytic and required for full virulence

Thomson, Euan L.S.; Dennis, Jonathan J.
Fonte: Landes Bioscience Publicador: Landes Bioscience
Tipo: Artigo de Revista Científica
Publicado em 01/05/2012 EN
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Members of the Burkholderia cepacia complex (Bcc) have recently gained notoriety as significant bacterial pathogens due to their extreme levels of antibiotic resistance, their transmissibility in clinics, their persistence in bacteriostatic solutions, and their intracellular survival capabilities. As pathogens, the Bcc are known to elaborate a number of virulence factors including proteases, lipases and other exoproducts, as well as a number of secretion system associated effectors. Through random and directed mutagenesis studies, we have identified a Bcc gene cluster capable of expressing a toxin that is both hemolytic and required for full Bcc virulence. The Bcc toxin is synthesized via a non-ribosomal peptide synthetase mechanism, and appears to be related to the previously identified antifungal compound burkholdine or occidiofungin. Further testing shows mutations to this gene cluster cause a significant reduction in both hemolysis and Galleria mellonella mortality. Mutation to a glycosyltransferase gene putatively responsible for a structural-functional toxin variant causes only partial reduction in hemolysis. Molecular screening identifies the Bcc species containing this gene cluster, of which several strains produce hemolytic activity.

Growth behaviour and mechanical properties of PLL/HA multilayer films studied by AFM

Üzüm, Cagri; Hellwig, Johannes; Madaboosi, Narayanan; Volodkin, Dmitry; von Klitzing, Regine
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 21/11/2012 EN
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Scanning- and colloidal-probe atomic force microscopy were used to study the mechanical properties of poly(L-lysine)/hyaluronan (PLL/HA)n films as a function of indentation velocity and the number of polymer deposition steps n. The film thickness was determined by two independent AFM-based methods: scratch-and-scan and newly developed full-indentation. The advantages and disadvantages of both methods are highlighted, and error minimization techniques in elasticity measurements are addressed. It was found that the film thickness increases linearly with the bilayer number n, ranging between 400 and 7500 nm for n = 12 and 96, respectively. The apparent Young’s modulus E ranges between 15 and 40 kPa and does not depend on the indenter size or the film bilayer number n. Stress relaxation measurements show that PLL/HA films have a viscoelastic behaviour, regardless of their thickness. If indentation is performed several times at the same lateral position on the film, a viscous/plastic deformation takes place.

Interpreting motion and force for narrow-band intermodulation atomic force microscopy

Platz, Daniel; Forchheimer, Daniel; Tholén, Erik A; Haviland, David B
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 21/01/2013 EN
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Intermodulation atomic force microscopy (ImAFM) is a mode of dynamic atomic force microscopy that probes the nonlinear tip–surface force by measurement of the mixing of multiple modes in a frequency comb. A high-quality factor cantilever resonance and a suitable drive comb will result in tip motion described by a narrow-band frequency comb. We show, by a separation of time scales, that such motion is equivalent to rapid oscillations at the cantilever resonance with a slow amplitude and phase or frequency modulation. With this time-domain perspective, we analyze single oscillation cycles in ImAFM to extract the Fourier components of the tip–surface force that are in-phase with the tip motion (F I) and quadrature to the motion (F Q). Traditionally, these force components have been considered as a function of the static-probe height only. Here we show that F I and F Q actually depend on both static-probe height and oscillation amplitude. We demonstrate on simulated data how to reconstruct the amplitude dependence of F I and F Q from a single ImAFM measurement. Furthermore, we introduce ImAFM approach measurements with which we reconstruct the full amplitude and probe-height dependence of the force components F I and F Q, providing deeper insight into the tip–surface interaction. We demonstrate the capabilities of ImAFM approach measurements on a polystyrene polymer surface.

New GABA amides activating GABAA-receptors

Raster, Peter; Späth, Andreas; Bultakova, Svetlana; Gorostiza, Pau; König, Burkhard; Bregestovski, Piotr
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 20/02/2013 EN
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We have prepared a series of new and some literature-reported GABA-amides and determined their effect on the activation of GABAA-receptors expressed in CHO cells. Special attention was paid to the purification of the target compounds to remove even traces of GABA contaminations, which may arise from deprotection steps in the synthesis. GABA-amides were previously reported to be partial, full or superagonists. In our hands these compounds were not able to activate GABAA-receptor channels in whole-cell patch-clamp recordings. New GABA-amides, however, gave moderate activation responses with a clear structure–activity relationship suggesting some of these compounds as promising molecular tools for the functional analysis of GABAA-receptors.

Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

Minko, Yury; Pasco, Morgane; Chechik, Helena; Marek, Ilan
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 13/03/2013 EN
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The carbocupration reactions of heterosubstituted alkynes allow the regio- and stereoselective formation of vinyl organometallic species. N-Alkynylamides (ynamides) are particularly useful substrates for the highly regioselective carbocupration reaction, as they lead to the stereodefined formation of vinylcopper species geminated to the amide moiety. The latter species are involved in numerous synthetically useful transformations leading to valuable building blocks in organic synthesis. Here we describe in full the results of our studies related to the carbometallation reactions of N-alkynylamides.

Introducing Spectral Structure Activity Relationship (S-SAR) Analysis. Application to Ecotoxicology

Putz, Mihai V.; Lacrămă, Ana-Maria
Fonte: Molecular Diversity Preservation International (MDPI) Publicador: Molecular Diversity Preservation International (MDPI)
Tipo: Artigo de Revista Científica
Publicado em 22/05/2007 EN
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A novel quantitative structure-activity (property) relationship model, namely Spectral-SAR, is presented in an exclusive algebraic way replacing the old-fashioned multi-regression one. The actual S-SAR method interprets structural descriptors as vectors in a generic data space that is further mapped into a full orthogonal space by means of the Gram-Schmidt algorithm. Then, by coordinated transformation between the data and orthogonal spaces, the S-SAR equation is given under simple determinant form for any chemical-biological interactions under study. While proving to give the same analytical equation and correlation results with standard multivariate statistics, the actual S-SAR frame allows the introduction of the spectral norm as a valid substitute for the correlation factor, while also having the advantage to design the various related SAR models through the introduced “minimal spectral path” rule. An application is given performing a complete S-SAR analysis upon the Tetrahymena pyriformis ciliate species employing its reported eco-toxicity activities among relevant classes of xenobiotics. By representing the spectral norm of the endpoint models against the concerned structural coordinates, the obtained S-SAR endpoints hierarchy scheme opens the perspective to further design the ecotoxicological test batteries with organisms from different species.

A study on electrospray mass spectrometry of fullerenol C60(OH)24

Silion, Mihaela; Dascalu, Andrei; Pinteala, Mariana; Simionescu, Bogdan C; Ungurenasu, Cezar
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 02/07/2013 EN
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Full characterization of fullerenol C60(OH)24 by HPLC ESI-MS in negative and positive ionization modes was achieved. Fragmentor voltage and capillary voltage were optimized in order to obtain a good signal stability and the best peak intensity distribution for the fullerenol C60(OH)24 in both negative and positive modes. While the predominant base peak observed for C60(OH)24 in the negative ionization mode was [M − H]− at m/z 1127, those observed in the positive mode were multiply charged [M − H2O + 4H]4+ at m/z 279 and [M − 12H2O + 2NH3 + 6H]6+ at m/z 158.

Synthesis of the calcilytic ligand NPS 2143

Johansson, Henrik; Cailly, Thomas; Rojas Bie Thomsen, Alex; Bräuner-Osborne, Hans; Sejer Pedersen, Daniel
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 09/07/2013 EN
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(R)-3 (NPS 2143) is a negative allosteric modulator of the human calcium-sensing receptor (CaSR) and as such represents an important pharmacological tool compound for studying the CaSR. Herein, we disclose for the first time a complete experimental description, detailed characterisation and assessment of enantiomeric purity for (R)-3. An efficient, reproducible and scalable synthesis of (R)-3 that requires a minimum of chromatographic purification steps is presented. (R)-3 was obtained in excellent optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature.

The longest mitochondrial RNA editing PPR protein MEF12 in Arabidopsis thaliana requires the full-length E domain

Härtel, Barbara; Zehrmann, Anja; Verbitskiy, Daniil; Takenaka, Mizuki
Fonte: Landes Bioscience Publicador: Landes Bioscience
Tipo: Artigo de Revista Científica
EN
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Mitochondrial RNA editing factor 12 (MEF12) was identified in a screen for editing defects of a chemically mutated plant population in Arabidopsis thaliana. The MEF12 editing protein is required for the C to U change of nucleotide nad5-374. The MEF12 polypeptide is characterized by an exceptionally long stretch of 25 pentatricopeptide repeats (PPR) and a C-terminal extension domain. Editing is lost in mutant plants with a stop codon in the extending element. A T-DNA insertion substituting the 10 C-terminal amino acids of the extension domain reduces RNA editing to about 20% at the target site in a mutant plant. These results support the importance of the full-length extension module for functional RNA editing in plant mitochondria.

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

Wojcik, Felix; Lel, Sinaida; O’Brien, Alexander G; Seeberger, Peter H; Hartmann, Laura
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 07/11/2013 EN
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We present the solid phase synthesis of carbohydrate-functionalized oligo(amidoamines) with different functionalization patterns utilizing a novel alphabet of six differently glycosylated building blocks. Highly efficient in flow conjugation of thioglycosides to a double-bond presenting diethylentriamine precursor is the key step to prepare these building blocks suitable for fully automated solid-phase synthesis. Introduction of the sugar ligands via functionalized building blocks rather than postfunctionalization of the oligomeric backbone allows for the straightforward synthesis of multivalent glycoligands with full control over monomer sequence and functionalization pattern. We demonstrate the potential of this building-block approach by synthesizing oligomers with different numbers and spacing of carbohydrates and also show the feasibility of heteromultivalent glycosylation patterns by combining building blocks presenting different mono- and disaccharides.

Halogenated volatiles from the fungus Geniculosporium and the actinomycete Streptomyces chartreusis

Wang, Tao; Rabe, Patrick; Citron, Christian A; Dickschat, Jeroen S
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 03/12/2013 EN
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Two unidentified chlorinated volatiles X and Y were detected in headspace extracts of the fungus Geniculosporium. Their mass spectra pointed to the structures of a chlorodimethoxybenzene for X and a dichlorodimethoxybenzene for Y. The mass spectra of some constitutional isomers for X and Y were included in our databases and proved to be very similar, thus preventing a full structural assignment. For unambiguous structure elucidation all possible constitutional isomers for X and Y were obtained by synthesis or from commercial suppliers. Comparison of mass spectra and GC retention times rigorously established the structures of the two chlorinated volatiles. Chlorinated volatiles are not very widespread, but brominated or even iodinated volatiles are even more rare. Surprisingly, headspace extracts from Streptomyces chartreusis contained methyl 2-iodobenzoate, a new natural product that adds to the small family of iodinated natural products.

A long non-coding RNA promotes full activation of adult gene expression in the chicken α-globin domain

Arriaga-Canon, Cristian; Fonseca-Guzmán, Yael; Valdes-Quezada, Christian; Arzate-Mejía, Rodrigo; Guerrero, Georgina; Recillas-Targa, Félix
Fonte: Landes Bioscience Publicador: Landes Bioscience
Tipo: Artigo de Revista Científica
EN
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Long non-coding RNAs (lncRNAs) were recently shown to regulate chromatin remodelling activities. Their function in regulating gene expression switching during specific developmental stages is poorly understood. Here we describe a nuclear, non-coding transcript responsive for the stage-specific activation of the chicken adult αD globin gene. This non-coding transcript, named α-globin transcript long non-coding RNA (lncRNA-αGT) is transcriptionally upregulated in late stages of chicken development, when active chromatin marks the adult αD gene promoter. Accordingly, the lncRNA-αGT promoter drives erythroid-specific transcription. Furthermore, loss of function experiments showed that lncRNA-αGT is required for full activation of the αD adult gene and maintenance of transcriptionally active chromatin. These findings uncovered lncRNA-αGT as an important part of the switching from embryonic to adult α-globin gene expression, and suggest a function of lncRNA-αGT in contributing to the maintenance of adult α-globin gene expression by promoting an active chromatin structure.

The role of surface corrugation and tip oscillation in single-molecule manipulation with a non-contact atomic force microscope

Wagner, Christian; Fournier, Norman; Tautz, F Stefan; Temirov, Ruslan
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 26/02/2014 EN
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Scanning probe microscopy (SPM) plays an important role in the investigation of molecular adsorption. The possibility to probe the molecule–surface interaction while tuning its strength through SPM tip-induced single-molecule manipulation has particularly promising potential to yield new insights. We recently reported experiments, in which 3,4,9,10-perylene-tetracarboxylic-dianhydride (PTCDA) molecules were lifted with a qPlus-sensor and analyzed these experiments by using force-field simulations. Irrespective of the good agreement between the experiment and those simulations, systematic inconsistencies remained that we attribute to effects omitted from the initial model. Here we develop a more realistic simulation of single-molecule manipulation by non-contact AFM that includes the atomic surface corrugation, the tip elasticity, and the tip oscillation amplitude. In short, we simulate a full tip oscillation cycle at each step of the manipulation process and calculate the frequency shift by solving the equation of motion of the tip. The new model correctly reproduces previously unexplained key features of the experiment, and facilitates a better understanding of the mechanics of single-molecular junctions. Our simulations reveal that the surface corrugation adds a positive frequency shift to the measurement that generates an apparent repulsive force. Furthermore...

Encapsulation of nanoparticles into single-crystal ZnO nanorods and microrods

Liu, Jinzhang; Notarianni, Marco; Rintoul, Llew; Motta, Nunzio
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 16/04/2014 EN
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One-dimensional single crystal incorporating functional nanoparticles of other materials could be an interesting platform for various applications. We studied the encapsulation of nanoparticles into single-crystal ZnO nanorods by exploiting the crystal growth of ZnO in aqueous solution. Two types of nanodiamonds with mean diameters of 10 nm and 40 nm, respectively, and polymer nanobeads with size of 200 nm have been used to study the encapsulation process. It was found that by regrowing these ZnO nanorods with nanoparticles attached to their surfaces, a full encapsulation of nanoparticles into nanorods can be achieved. We demonstrate that our low-temperature aqueous solution growth of ZnO nanorods do not affect or cause degradation of the nanoparticles of either inorganic or organic materials. This new growth method opens the way to a plethora of applications combining the properties of single crystal host and encapsulated nanoparticles. We perform micro-photoluminescence measurement on a single ZnO nanorod containing luminescent nanodiamonds and the spectrum has a different shape from that of naked nanodiamonds, revealing the cavity effect of ZnO nanorod.

KIAA1114, a full-length protein encoded by the trophinin gene, is a novel surface marker for isolating tumor-initiating cells of multiple hepatocellular carcinoma subtypes

Kim, Sae Won; Yang, Hyun Gul; Kang, Moon Cheol; Lee, Seungwon; Namkoong, Hong; Lee, Seung-Woo; Sung, Young Chul
Fonte: Impact Journals LLC Publicador: Impact Journals LLC
Tipo: Artigo de Revista Científica
Publicado em 31/03/2014 EN
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Identification of novel biomarkers for tumor-initiating cells (TICs) is of critical importance for developing diagnostic and therapeutic strategies against cancers. Here we identified the role of KIAA1114, a full-length translational product of the trophinin gene, as a distinctive marker for TICs in human liver cancer by developing a DNA vaccine-induced monoclonal antibody targeting the putative extracellular domain of KIAA1114. Compared with other established markers of liver TICs, KIAA1114 was unique in that its expression was detected in both alpha fetoprotein (AFP)-positive and AFP-negative hepatocellular carcinoma (HCC) cell lines with the expression levels of KIAA1114 being positively correlated to their tumorigenic potentials. Notably, KIAA1114 expression was strongly detected in primary hepatic tumor, but neither in the adjacent non-tumorous tissue from the same patient nor normal liver tissue. KIAA1114high cells isolated from HCC cell lines displayed TIC-like features with superior functional and phenotypic traits compared to their KIAA1114low counterparts, including tumorigenic abilities in xenotransplantation model, in vitro colony- and spheroid-forming capabilities, expression of stemness-associated genes, and migratory capacity. Our findings not only address the value of a novel antigen...

Androgen receptor splice variants activating the full-length receptor in mediating resistance to androgen-directed therapy

Cao, Bo; Qi, Yanfeng; Zhang, Guanyi; Xu, Duo; Zhan, Yang; Alvarez, Xavier; Guo, Zhiyong; Fu, Xueqi; Plymate, Stephen R.; Sartor, Oliver; Zhang, Haitao; Dong, Yan
Fonte: Impact Journals LLC Publicador: Impact Journals LLC
Tipo: Artigo de Revista Científica
Publicado em 04/03/2014 EN
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Upregulation of constitutively-active androgen receptor splice variants (AR-Vs) has been implicated in AR-driven tumor progression in castration-resistant prostate cancer. To date, functional studies of AR-Vs have been focused mainly on their ability to regulate gene expression independent of the full-length AR (AR-FL). Here, we showed that AR-V7 and ARv567es, two major AR-Vs, both facilitated AR-FL nuclear localization in the absence of androgen and mitigated the ability of the antiandrogen enzalutamide to inhibit AR-FL nuclear trafficking. AR-V bound to the promoter of its specific target without AR-FL, but co-occupied the promoter of canonical AR target with AR-FL in a mutually-dependent manner. AR-V expression attenuated both androgen and enzalutamide modulation of AR-FL activity/cell growth, and mitigated the in vivo antitumor efficacy of enzalutamide. Furthermore, ARv567es levels were upregulated in xenograft tumors that had acquired enzalutamide resistance. Collectively, this study highlights a dual function of AR-Vs in mediating castration resistance. In addition to trans-activating target genes independent of AR-FL, AR-Vs can serve as a “rheostat” to control the degree of response of AR-FL to androgen-directed therapy via activating AR-FL in an androgen-independent manner. The findings shed new insights into the mechanisms of AR-V-mediated castration resistance and have significant therapeutic implications.

Theoretical studies on the intramolecular cyclization of 2,4,6-t-Bu3C6H2P=C: and effects of conjugation between the P=C and aromatic moieties

Yoshifuji, Masaaki; Ito, Shigekazu
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 07/05/2014 EN
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The intramolecular C–H insertion of the Mes*-substituted phosphanylidenecarbene [Mes*P=C:] (Mes* = 2,4,6-t-Bu3C6H2) and physicochemical properties of the cyclized product, 6,8-di-tert-butyl-3,4-dihydro-4,4-dimethyl-1-phosphanaphthalene were studied based on ab initio calculations. Whereas the alternative Fritsch–Buttenberg–Wiechell-type rearrangement requires almost no activation energy, the intramolecular cyclization needs an activation energy of 12.3 kcal/mol at the MP2(full)/6-31G(d) condition. DFT calculations supported that the optimized structure of the cyclization product of Mes*P=C: suggests remarkable conjugation effects between the nearly coplanar P=C skeleton and the aryl moiety.

Designing magnetic superlattices that are composed of single domain nanomagnets

Forrester, Derek M; Kusmartsev, Feodor V; Kovács, Endre
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 03/07/2014 EN
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Background: The complex nature of the magnetic interactions between any number of nanosized elements of a magnetic superlattice can be described by the generic behavior that is presented here. The hysteresis characteristics of interacting elliptical nanomagnets are described by a quasi-static method that identifies the critical boundaries between magnetic phases. A full dynamical analysis is conducted in complement to this and the deviations from the quasi-static analysis are highlighted. Each phase is defined by the configuration of the magnetic moments of the chain of single domain nanomagnets and correspondingly the existence of parallel, anti-parallel and canting average magnetization states.

Towards bottom-up nanopatterning of Prussian blue analogues

Trannoy, Virgile; Faustini, Marco; Grosso, David; Mazerat, Sandra; Brisset, François; Dazzi, Alexandre; Bleuzen, Anne
Fonte: Beilstein-Institut Publicador: Beilstein-Institut
Tipo: Artigo de Revista Científica
Publicado em 31/10/2014 EN
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Ordered nanoperforated TiO2 monolayers fabricated through sol–gel chemistry were used to grow isolated particles of Prussian blue analogues (PBA). The elaboration of the TiO2/CoFe PBA nanocomposites involves five steps. The samples were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), infrared spectroscopy and X-ray photoelectron spectroscopy (XPS) all along the synthesis process. Selected physico-chemical parameters have been varied in order to determine the key steps of the synthesis process and to optimize it. This study is an important step towards the full control of the fabrication process.

Rapid continuous microwave-assisted synthesis of silver nanoparticles to achieve very high productivity and full yield: from mechanistic study to optimal fabrication strategy

Dzido, Grzegorz; Markowski, Piotr; Małachowska-Jutsz, Anna; Prusik, Krystian; Jarzębski, Andrzej B.
Fonte: Springer Netherlands Publicador: Springer Netherlands
Tipo: Artigo de Revista Científica
EN
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Systematic studies of silver nanoparticle synthesis in a continuous-flow single-mode microwave reactor using polyol process were performed, revealing that the synthesis is exceptionally effective to give very small metal particles at full reaction yield and very high productivity. Inlet concentration of silver nitrate or silver acetate, applied as metal precursors, varied between 10 and 50 mM, and flow rates ranged from 0.635 to 2.5 dm3/h, to give 3–24 s reaction time. Owing to its much higher reactivity, silver acetate was shown to be far superior substrate for the synthesis of small (10–20 nm) spherical silver nanoparticles within a few seconds. Its restricted solubility in ethylene glycol, applied as the solvent and reducing agent, appeared to be vital for effective separation of the stage of particle growth from its nucleation to enable rapid synthesis of small particles in a highly loaded system. This was not possible to obtain using silver nitrate. All the observations could perfectly be explained by a classical LaMer–Dinegar model of NPs’ formation, but taking into account also nonisothermal character of the continuous-flow process and acetate dissolution in the reaction system. The performed studies indicate an optimal strategy for the high-yield fabrication of metal particles using polyol method.