Secondary atomization of a biodiesel micro-emulsion fuel droplet colliding with a heated wall

Using high-speed video recording, we establish the following regimes of hydrodynami

Role of Polyamine-Induced Dimerization of Antizyme in Its Cellular Functions

Funding: This work was supported by grants from the Russian Science Foundation (grant # 17-74-20049—synthesis of C-methylated Spd analogues, ITC studies of dimerization of OAZ1, and frameshifting experiments), the Russian Science Foundation (grant # 19-74-10086—isolation of OAZ1, electrophoresis studies of dimerization of OAZ1), and the Academy of Finland (grants # 292574 and # 315487). Acknowledgments: The authors thank A. Karppinen, A. Korhonen, T. Reponen, M. Salminkoski, and S.D. Negrya for their skillful technical assistance.Peer reviewedPublisher PD

The Essential Role of Spermidine in Growth of <i>Agrobacterium tumefaciens</i> Is Determined by the 1,3-Diaminopropane Moiety

The ubiquitous polyamine spermidine is indispensable for eukaryotic growth and cell proliferation. A conserved vital function of spermidine across eukaryotes is conferred by its aminobutyl group that is transferred to a single lysine in translation factor eIF5A to form the essential hypusine post-translational modification required for cellular translation. In direct contrast, although spermidine is absolutely essential for growth of α-proteobacterial plant pathogen <i>Agrobacterium tumefaciens</i>, we have found, by employing a suite of natural polyamines and synthetic methylated spermidine analogues together with spermidine biosynthetic mutants, that it is solely the 1,3-diaminopropane moiety of spermidine that is required for growth. Indeed, any polyamine containing an intact terminal 1,3-diaminopropane moiety can replace spermidine for growth, including the simple diamine 1,3-diaminopropane itself, a paradigm shift in understanding polyamine function in bacteria. We have identified for the first time a spermidine retroconversion activity in bacteria, producing diamine putrescine from triamine spermidine; however, exogenously supplied tetraamine spermine is resistant to retroconversion. When spermidine levels are pharmacologically decreased, synthesis of spermine from spermidine is induced via the same biosynthetic enzymes, carboxyspermidine dehydrogenase and carboxyspermidine decarboxylase that produce spermidine from putrescine, the first identification of a spermine biosynthetic pathway in bacteria. This also suggests that spermidine represses spermine biosynthesis, but when spermidine levels decrease, it is then converted by carboxyspermidine dehydrogenase and decarboxylase enzymes to spermine, which is resistant to retroconversion and constitutes a sequestered pool of protected 1,3-diaminopropane modules required for growth. We also identify an efficient <i>N</i>-acetylspermidine deacetylase activity, indicative of a sophisticated bacterial polyamine homeostasis system

Difluoromethylornithine rebalances aberrant polyamine ratios in Snyder–Robinson syndrome

Abstract Snyder–Robinson syndrome (SRS) results from mutations in spermine synthase (SMS), which converts the polyamine spermidine into spermine. Affecting primarily males, common manifestations of SRS include intellectual disability, osteoporosis, hypotonia, and seizures. Symptom management is the only treatment. Reduced SMS activity causes spermidine accumulation while spermine levels are reduced. The resulting exaggerated spermidine:spermine ratio is a biochemical hallmark of SRS that tends to correlate with symptom severity. Our studies aim to pharmacologically manipulate polyamine metabolism to correct this imbalance as a therapeutic strategy for SRS. Here we report the repurposing of 2‐difluoromethylornithine (DFMO), an FDA‐approved inhibitor of polyamine biosynthesis, in rebalancing spermidine:spermine ratios in SRS patient cells. Mechanistic in vitro studies demonstrate that, while reducing spermidine biosynthesis, DFMO also stimulates the conversion of spermidine into spermine in hypomorphic SMS cells and induces uptake of exogenous spermine, altogether reducing the aberrant ratios. In a Drosophila SRS model characterized by reduced lifespan, DFMO improves longevity. As nearly all SRS patient mutations are hypomorphic, these studies form a strong foundation for translational studies with significant therapeutic potential

A desmethylphosphinothricin dipeptide derivative effectively inhibits Escherichia coli and Bacillus subtilis growth

New antibiotics are unquestionably needed to fight the emergence and spread of multidrugresistant bacteria. To date, antibiotics targeting bacterial central metabolism have been poorly investigated. By determining the minimal inhibitory concentration (MIC) of desmethylphosphinothricin (Glu-γ-PH), an analogue of glutamate with a phosphinic moiety replacing the γ-carboxyl group, we previously showed its promising antibacterial activity on Escherichia coli. Herein, we synthetized and determined the growth inhibition exerted on E. coli by an L-Leu dipeptide derivative of Glu-γ-PH (L-Leu-D,L-Glu-γ-PH). Furthermore, we compared the growth inhibition obtained with this dipeptide with that exerted by the free amino acid, i.e., Glu-γ-PH, and by their phosphonic and non-desmethylated analogues. All the tested compounds were more effective when assayed in a chemically-defined minimal medium. The dipeptide L-Leu-D,L-Glu-γ-PH had a significantly improved antibacterial activity (2 µg/mL), at a concentration between the non-desmethytaled (0.1 µg/mL) and the phosphonic (80 µg/mL) analogues. Also, in Bacillus subtilis, the dipeptide L-Leu-D,L-Glu-γ-PH displayed an activity comparable to that of the antibiotic amoxicillin. This work highlights the antibacterial relevance of the phosphinic pharmacophore and proposes new avenues for the development of novel antimicrobial drugs containing the phosphinic moiety

Hot Deformation Behavior of Novel Al-Cu-Y(Er)-Mg-Mn-Zr Alloys

The compression tests in a temperature range of 400–540 °C and strain rates of 0.1–15 s−1 were applied to novel Al-Cu-Y(Er)-Mg-Mn-Zr alloys to investigate their hot deformation behavior. The higher volume fraction of the intermetallic particles with a size of 0.5–4 µm in the alloys caused an increase in flow stress. Hyperbolic sine law constitutive models were constructed for the hot deformation behavior of Al-Cu-Y(Er)-Mg-Mn-Zr alloys. Effective activation energy has a higher value in the alloys with Er than in the alloys with Y. According to the processing maps, the temperature range of 420–480 °C and strain rates higher than 5 s−1 are the most unfavorable region for hot deformation for the investigated alloys. The deformation at 440 °C and 15 s−1 led to cracks on the surface of the sample. However, internal cracks were not observed in the microstructure after deformation. The optimum hot deformation temperatures were in a range of 500–540 °C and at strain rates of 0.1–15 s−1

Novel convenient synthesis of biologically active esters of hydroxylamine

Alkylation of ethyl N-hydroxyacetimidate with readily available methanesulfonates of functionally substituted alcohols and subsequent deprotection of aminooxy group is a novel and convenient method to prepare functionally substituted esters of hydroxylamine with high overall yield. This approach is a good alternative to well-known reaction of N-hydroxyphthalimide with alcohols under the Mitsunobu conditions. The properties of ethoxyethylidene protection of aminooxy group on the contrary to that of N-alkoxyphthalimide group allow to perform a wide spectra of the transformations in the radical of N-protected hydroxylamine derivatives. This is essential for synthetic strategies consisting in the introduction of N-protected aminooxy group at one of the first steps of synthesis and subsequent transformations of the radical. The inhibitory effect of one of the newly synthesized compound, 1-guanidinooxy-3-aminopropane (GAPA), was compared with that of well-known inhibitors of ornithine decarboxylase namely, α-difluoromethylornithine (DFMO) and 1-aminooxy-3-aminopropane (APA) on Leishmania donovani, a protozoan parasite that causes visceral leishmaniasis. GAPA, on the contrary with APA and DFMO, in micromolar concentrations, inhibited the growth of both amastigotes and promastigotes of sodium antimony gluconate-resistant forms of L. donovani