A stereospecific one-pot synthesis of β-chloro esters via the BiCl<inf>3</inf> catalysed O-acylative cleavage of crowded epoxides

© 2015, Science Reviews 2000 Ltd. All rights reserved. A simple, one-pot procedure is described for the stereospecific preparation of β-chloro esters from the corresponding crowded epoxide

The hydrolysis of geminal ethers: A kinetic appraisal of orthoesters and ketals

© 2016 Repetto et al. A novel approach to protecting jet fuel against the effects of water contamination is predicated upon the coupling of the rapid hydrolysis reactions of lipophilic cyclic geminal ethers, with the concomitant production of a hydrophilic acyclic hydroxyester with de-icing properties (Fuel Dehydrating Icing Inhibitors - FDII). To this end, a kinetic appraisal of the hydrolysis reactions of representative geminal ethers was undertaken using a convenient surrogate for the fuel-water interface (D2 O/CD3 CN 1:4). We present here a library of acyclic and five/six-membered cyclic geminal ethers arranged according to their hydroxonium catalytic coefficients for hydrolysis, providing for the first time a framework for the development of FDII. A combination of 1H NMR, labelling and computational studies was used to assess the effects that may govern the observed relative rates of hydrolyses

Automated Inspection Device for Explosive Charge in Shells - AIDECS

Certain defects in the explosive charge of an artillery shell can cause the projectile to explode prematurely in the barrel of the launcher from which it is fired. The sensitivity of the radiographic technique presently used is limited by the large influence of the steel shell casing on the transmitted radiation. A filmless radiometric technique utilizing the basic radiation principle of Compton scattering, which will detect cavities in the explosive filler with minimal interference from the steel casing, has been identified and tested. By scanning the shell with a beam of radiation and observing the Compton scattering through a unique collimating system, it has been possible to detect voids as small as 1/16 inch in cross section. The hardware consists of the source, beam collimator, detector collimator, and a large plastic scintillator detector system. The projectile is inserted into the beam path and moved through a fixed scanning pattern by a mechanical handling system. The scanning sequence is computer contra ll ed and results in a threedimensional data matrix giving a direct representation of density within the projectile. Voids are identified and classified by computer analysis, and shell acceptability decisions are automatically generated. An engineering prototype system is currently being assembled and tested. (A production prototype conceptual design is concurrently under development.) This new technique will replace an existing film radiography inspection procedure and eliminate the need for human interpretation of the defects, while providing more consistent and reliable inspections at lower costs

Peroxisomes:New insights into protein sorting, dynamics, quality control, signalling and roles in health and disease

The 6th Open European peroxisome meeting (OEPM) was held on the 26th and 27th of October (2018) in Groningen, the Netherlands. OEPM is a biannual meeting organized by a European peroxisome research group. Previous meetings were held in Leuven, BE (2006), Lunteren, NL (2010), Dijon, FR (2012), Neuss, GER (2014) and Vienna, AU (2016). Over 120 participants were registered from 14 European countries, as well as Israel, Canada, the USA and South Korea. A large number of European research groups participated, including established and younger groups, showing that peroxisome research is blooming in Europe. This will further expand with the EU Marie Curie Innovative training network PERICO (PERoxisome Interactions and COmmunication; http://www.itn-PERICO.eu; coordinated by Ida van der Klei), which recently started and aims to train the next generation of peroxisome researchers

Estimating absolute methylation levels at single-CpG resolution from methylation enrichment and restriction enzyme sequencing methods

Recent advancements in sequencing-based DNA methylation profiling methods provide an unprecedented opportunity to map complete DNA methylomes. These include whole-genome bisulfite sequencing (WGBS, MethylC-seq, or BS-seq), reduced-representation bisulfite sequencing (RRBS), and enrichment-based methods such as MeDIP-seq, MBD-seq, and MRE-seq. These methods yield largely comparable results but differ significantly in extent of genomic CpG coverage, resolution, quantitative accuracy, and cost, at least while using current algorithms to interrogate the data. None of these existing methods provides single-CpG resolution, comprehensive genome-wide coverage, and cost feasibility for a typical laboratory. We introduce methylCRF, a novel conditional random fields–based algorithm that integrates methylated DNA immunoprecipitation (MeDIP-seq) and methylation-sensitive restriction enzyme (MRE-seq) sequencing data to predict DNA methylation levels at single-CpG resolution. Our method is a combined computational and experimental strategy to produce DNA methylomes of all 28 million CpGs in the human genome for a fraction (<10%) of the cost of whole-genome bisulfite sequencing methods. methylCRF was benchmarked for accuracy against Infinium arrays, RRBS, WGBS sequencing, and locus-specific bisulfite sequencing performed on the same human embryonic stem cell line. methylCRF transformation of MeDIP-seq/MRE-seq was equivalent to a biological replicate of WGBS in quantification, coverage, and resolution. We used conventional bisulfite conversion, PCR, cloning, and sequencing to validate loci where our predictions do not agree with whole-genome bisulfite data, and in 11 out of 12 cases, methylCRF predictions of methylation level agree better with validated results than does whole-genome bisulfite sequencing. Therefore, methylCRF transformation of MeDIP-seq/MRE-seq data provides an accurate, inexpensive, and widely accessible strategy to create full DNA methylomes

Peroxisomal ACBD4 interacts with VAPB and promotes ER-peroxisome associations

Cooperation between cellular organelles such as mitochondria, peroxisomes and the ER is essential for a variety of important and diverse metabolic processes. Effective communication and metabolite exchange requires physical linkages between the organelles, predominantly in the form of organelle contact sites. At such contact sites organelle membranes are brought into close proximity by the action of molecular tethers, which often consist of specific protein pairs anchored in the membrane of the opposing organelles. Currently numerous tethering components have been identified which link the ER with multiple other organelles but knowledge of the factors linking the ER with peroxisomes is limited. Peroxisome-ER interplay is important because it is required for the biosynthesis of unsaturated fatty acids, ether-phospholipids and sterols with defects in these functions leading to severe diseases. Here, we characterize acyl-CoA binding domain protein 4 (ACBD4) as a tail-anchored peroxisomal membrane protein which interacts with the ER protein, vesicle-associated membrane protein-associated protein–B (VAPB) to promote peroxisome-ER associations

Association of CD4 Cell Depletion and Elevated Blood and Seminal Plasma Human Immunodeficiency Virus Type 1 (HIV-1) RNA Concentrations with Genital Ulcer Disease in HIV-1-Infected Men in Malawi

CD4 cell counts and blood plasma and seminal plasma human immunodeficiency virus type 1 (HIV-1) concentrations were compared in HIV-1 RNA-seropositive men with urethritis and with or without genital ulcer disease (GUD). GUD was associated with lower CD4 cell counts (median, 258 vs. 348/μL) and increased blood plasma HIV-1 RNA (median, 240 × 103 vs. 79.4 × 103 copies/ mL). Men with nongonococcal urethritis and GUD shed significantly greater quantities of HIV-1 in semen (median, 195 × 103 vs. 4.0 × 103 copies/mL) than men with nongonococcal urethritis without GUD. These levels decreased ∽4-fold following antibiotic therapy. The results indicate an association between GUD and increased blood HIV-1 RNA levels. Increased HIV-1 in semen was demonstrated in some men with GUD; such an increase could lead to increased transmission, thus complicating interpretation of the role of the genital ulcer itself in the infectiousness of HIV. Reasons for increased HIV RNA in semen in men with GUD remain to be determine

Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer

Intracellular levels of zinc have shown a strong inverse correlation to growth and malignancy of prostate cancer. To date, studies of zinc supplementation in prostate cancer have been equivocal and have not accounted for bioavailability of zinc. Therefore, we hypothesized that direct intra-tumoral injection of zinc could impact prostate cancer growth. In this study, we evaluated the cytotoxic properties of the pH neutral salt zinc acetate on the prostate cancer cell lines PC3, DU145 and LNCaP. Zinc acetate killed prostate cancer cell lines in vitro, independent of androgen sensitivity, in a dose-dependent manner in a range between 200 and 600 μM. Cell death occurred rapidly with 50% cell death by six hours and maximal cell death by 18 hours. We next established a xenograft model of prostate cancer and tested an experimental treatment protocol of direct intra-tumoral injection of zinc acetate. We found that zinc treatments halted the growth of the prostate cancer tumors and substantially extended the survival of the animals, whilst causing no detectable cytoxicity to other tissues. Thus, our studies form a solid proof-of-concept that direct intra-tumoral injection of zinc acetate could be a safe and effective treatment strategy for prostate cancer

Dual Action Additives for Jet A-1: Fuel Dehydrating Icing Inhibitors

© 2016 American Chemical Society. A novel approach for protecting jet fuel against the effects of water contamination based upon Fuel Dehydrating Icing Inhibitors (FDII) is presented. This dual-action strategy is predicated on the addition of a fuel-soluble water scavenger that undergoes a kinetically fast hydrolysis reaction with free water to produce a hydrophilic ice inhibitor, thereby further militating against the effects of water crystallization. Criteria for an optimum FDII were identified and then used to screen a range of potential water-scavenging agents, which led to a closer examination of systems based upon exo/endo-cyclic ketals and both endo- and exo-cyclic ortho esters. The ice inhibition properties of the subsequent products of the hydrolysis reaction in Jet A-1 were screened by differential scanning calorimetry. The hydrolysis products of 2-methoxy-2-methyl-1,3-dioxolane demonstrate similar ice inhibition performance to DiEGME over a range of blend levels. The calorific values for the products of hydrolysis were also investigated, and it is clear that there would be a significant fuel saving on use of the additive over current fuel system icing inhibitors. Finally, three promising candidates, 2-methoxy-2-methyl-1,3-dioxolane, 2-methoxy-2-methyl-1,3-dioxane, and 2-methoxy-2,4,5-trimethyl-1,3-dioxolane, were shown to effectively dehydrate Jet A-1 at room temperature over a 2 h period