(+)‐Gibberellin C: hydrogen‐bonding pattern of the monohydrate of a non‐racemic pentacyclic diterpenoid

In the monohydrate of the title compound, (+)‐2β,4aα‐di­hydroxy‐1,7‐di­methyl‐8‐oxo‐4bβ,7α‐gibbane‐1α,10β‐di­carb­ox­yl­ic acid‐1,4a‐lactone, C₁₉H₂₄O₆·H₂O, intermolecular hydrogen bonding progresses helically along b from carboxyl to ketone [O?O = 2.694 (5) Å]. The carboxyl and lactone carbonyl groups in translationally related mol­ecules within a helix both accept hydrogen bonds from the same water of hydration. The oxy­gen of this water in turn accepts a hydrogen bond from the hydroxyl group of a third screw‐related mol­ecule in an adjacent counterdirectionally oriented helix, yielding a complex three‐dimensional hydrogen‐bonding array. Intermolecular O?H—C close contacts were found to the carboxyl and lactone carbonyls, the hydroxyl, and the water.     

Muscle spindles are concentrated in the superior vocalis subcompartment of the human thyroarytenoid muscle

It is hypothesized that different parts of the thyroarytenoid muscle (TA) are functionally specialized. Specifically, the TA is divided into a lateral muscularis compartment and a medial vocalis compartment. This study examined the distribution of muscle spindles throughout the human TA as an indicator of these functional differences. Histological cross-sections from the anterior, middle, and posterior regions of five human membranous vocal folds were examined for the number and location of muscle spindles. There was an average of 6.1 muscle spindles in sections from each region with no significant variation between the different regions (p < .05). However, in sections from all three regions, the muscle spindles were always found to be concentrated in the superior medial quadrant of the TA (mean 85.9%, p < .01). The inferior medial, superior lateral, and inferior lateral quadrants of the TA contained 11.96%, 2.17%, and 0%, respectively, of the total muscle spindles. Within the superior medial quadrant, most of the muscle spindles were localized in the most superficial part of the muscle.The results of this study demonstrate that the majority of TA muscle spindlesare concentrated in its superior medial quadrant, an area we have termed the superior vocalis subcompartment (SC. This finding suggests that the superior vocalis SC is functionally distinct from the remainder of the TA. It is hypothesized that tension in the superior vocalis SC can be controlled independently from the remainder of the TA, and this capability is used to effect the biomechanics of vocal fold vibration during phonation.     

Edge colorings of graphs embeddable in a surface of low genus

In this paper, by using the Discharging Method, we show that any graph with maximum degree Δ 8 that is embeddable in a surface Σ of characteristic χ(Σ) 0 is class one and any graph with maximum degree Δ 9 that is embeddable in a surface Σ of characteristic χ(Σ) = − 1 is class one. For surfaces of characteristic 0 or −1, these results improve earlier results of Mel'nikov.     

Mono‐, di‐ and trimethylated homologues of isoprenoid tetraether lipid cores in archaea and environmental samples: mass spectrometric identification and significance

Higher homologues of widely reported C₈₆ isoprenoid diglycerol tetraether lipid cores, containing 0–6 cyclopentyl rings, have been identified in (hyper)thermophilic archaea, representing up to 21% of total tetraether lipids in the cells. Liquid chromatography‐tandem mass spectrometry confirms that the additional carbon atoms in the C_87‐88 homologues are located in the etherified chains. Structures identified include dialkyl and monoalkyl (‘H‐shaped’) tetraethers containing C_40‐42 or C_81‐82 hydrocarbons, respectively, many representing novel compounds. Gas chromatography‐mass spectrometric analysis of hydrocarbons released from the lipid cores by ether cleavage suggests that the C₄₀ chains are biphytanes and the C₄₁ chains 13‐methylbiphytanes. Multiple isomers, having different chain combinations, were recognised among the dialkyl lipids. Methylated tetraethers are produced by Methanothermobacter thermautotrophicus in varying proportions depending on growth conditions, suggesting that methylation may be an adaptive mechanism to regulate cellular function. The detection of methylated lipids in Pyrobaculum sp. AQ1.S2 and Sulfolobus acidocaldarius represents the first reported occurrences in Crenarchaeota. Soils and aquatic sediments from geographically distinct mesotemperate environments that were screened for homologues contained monomethylated tetraethers, with di‐ and trimethylated structures being detected occasionally. The structural diversity and range of occurrences of the C_87‐89 tetraethers highlight their potential as complementary biomarkers for archaea in natural environments. Copyright © 2015 John Wiley & Sons, Ltd.     

TEMPO-Assisted Free Radical-Initiated Peptide Sequencing Mass Spectrometry (FRIPS MS) in Q-TOF and Orbitrap Mass Spectrometers: Single-Step Peptide Backbone Dissociations in Positive Ion Mode

The present study demonstrates that one-step peptide backbone fragmentations can be achieved using the TEMPO [2-(2,2,6,6-tetramethyl piperidine-1-oxyl)]-assisted free radical-initiated peptide sequencing (FRIPS) mass spectrometry in a hybrid quadrupole time-of-flight (Q-TOF) mass spectrometer and a Q-Exactive Orbitrap instrument in positive ion mode, in contrast to two-step peptide fragmentation in an ion-trap mass spectrometer (reference Anal. Chem. 85, 7044–7051 (30)). In the hybrid Q-TOF and Q-Exactive instruments, higher collisional energies can be applied to the target peptides, compared with the low collisional energies applied by the ion-trap instrument. The higher energy deposition and the additional multiple collisions in the collision cell in both instruments appear to result in one-step peptide backbone dissociations in positive ion mode. This new finding clearly demonstrates that the TEMPO-assisted FRIPS approach is a very useful tool in peptide mass spectrometry research.

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A substrate-free activity-based protein profiling screen for the discovery of selective PREPL inhibitors

Peptidases play vital roles in physiology through the biosynthesis, degradation, and regulation of peptides. Prolyl endopeptidase-like (PREPL) is a newly described member of the prolyl peptidase family, with significant homology to mammalian prolyl endopeptidase and the bacterial peptidase oligopeptidase B. The biochemistry and biology of PREPL are of fundamental interest due to this enzyme's homology to the biomedically important prolyl peptidases and its localization in the central nervous system. Furthermore, genetic studies of patients suffering from hypotonia-cystinuria syndrome (HCS) have revealed a deletion of a portion of the genome that includes the PREPL gene. HCS symptoms thought to be caused by lack of PREPL include neuromuscular and mild cognitive deficits. A number of complementary approaches, ranging from biochemistry to genetics, will be required to understand the biochemical, cellular, physiological, and pathological mechanisms regulated by PREPL. We are particularly interested in investigating physiological substrates and pathways controlled by PREPL. Here, we use a fluorescence polarization activity-based protein profiling (fluopol-ABPP) assay to discover selective small-molecule inhibitors of PREPL. Fluopol-ABPP is a substrate-free approach that is ideally suited for studying serine hydrolases for which no substrates are known, such as PREPL. After screening over 300,000 compounds using fluopol-ABPP, we employed a number of secondary assays to confirm assay hits and characterize a group of 3-oxo-1-phenyl-2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitrile and 1-alkyl-3-oxo-3,5,6,7-tetrahydro-2H-cyclopenta[c]pyridine-4-carbonitrile PREPL inhibitors that are able to block PREPL activity in cells. Moreover, when administered to mice, 1-isobutyl-3-oxo-3,5,6,7-tetrahydro-2H-cyclopenta[c]pyridine-4-carbonitrile distributes to the brain, indicating that it may be useful for in vivo studies. The application of fluopol-ABPP has led to the first reported PREPL inhibitors, and these inhibitors will be of great value in studying the biochemistry of PREPL and in eventually understanding the link between PREPL and HCS.     

A pyrene-based fluorescent sensor for Zn2+ ions: a molecular 'butterfly'

A simple pyrene-based triazole receptor has been synthesised and shown to self-assemble in the presence of ZnCl(2) in an exclusively 2:1 ratio, whereas a mixture of 2:1 and 1:1 ratios are observed for other Zn(2+) salts. The pyrene units are syn in orientation; this is supported by a strong excimer signal observed at 410 nm in the presence of ZnCl(2) in acetonitrile. DFT calculations and 2D NMR support the proposed structure.     

Integration of a macro/micro architectured compartmentalised neuronal culture device using a rapid prototyping moulding process

The rapid prototyping of a reversible and one step moulded compartmentalised neuron glass/PDMS device with a thin wall barrier directly adjacent to the reservoirs is presented. A simple moulding technique to produce these devices results in a barrier of 560 μm where the 3 μm deep by 8 μm wide channels can be reversibly fabricated in either the glass base or PDMS compartmentalised mould depending on the type of application required. Using glass substrates with commercially laser engraved microchannels, both the PDMS planar and PDMS channelled device can be easily fabricated in a standard laboratory. The compartmentalised device has several advantages including good experimental accessibility and versatility with a variety of end user applications.     

Activity of Cuban propolis extracts on Leishmania amazonensis and Trichomonas vaginalis

In this paper we analyzed the antiprotozoal effects of eighteen Cuban propolis extracts (brown, red and yellow type) collected in different geographic areas, using Leishmania amazonensis (as a model of intracellular protozoa) and Trichomonas vaginalis (as a model of extracellular protozoa). All evaluated propolis extracts caused inhibitory effect on intracellular amastigotes of L. amazonensis. However, cytotoxicity on peritoneal macrophages from BALB/c mice was observed. Only five samples decreased the viability of T. vaginalis trophozoites at concentrations lower than 10 microg/mL. No correlation between the type of propolis and antiprotozoal activity was found. Cuban propolis extracts demonstrated activity against both intracellular and extracellular protozoa model, as well as the potentialities of propolis as a natural source to obtain new antiprotozoal agents.