The Curious Case of Article 281: A “Super” Provision within UNCLOS?

This article discusses the issue of treaty regimes in parallel to the United Nations Convention on the Law of the Sea in respect of peaceful settlement of disputes concerning the interpretation or application of the Convention. The duality in relevancy of such disputes to two treaties at the same time would have begged the question about which treaty should be applied to settle them, but UNCLOS has a clear, conflict-of-law style rules in place to address the question. Article 281(1) is one such rule, and, with its exclusionary effect, stands out as a super provision of the Convention.     

Long-term calorie restriction has minimal impact on brain metabolite and fatty acid profiles in aged rats on a Western-style diet

The effect of long-term calorie restriction (CR) on metabolites, fatty acid profiles and energy substrate transporter expression in the brain was assessed in aged rats. Three groups of male Sprague–Dawley rats were studied: (i) a 2 month old ad libitum-fed (2AL group), (ii) a 19 month old ad libitum-fed (19AL group), and (iii) a 19 month old group subjected to 40% CR from the age of 7.5 to 19 months (19CR group). The diet contained high sucrose and low n-3 polyunsaturated fatty acids (PUFA) so as to imitate a Western-style diet. High resolution magic angle spinning-¹H NMR showed an effect of aging on brain cortex metabolites compared to 2AL rats, the largest differences being for myo-inositol (+251% and +181%), lactate (+203% and +188%), β-hydroxybutyrate (+176% and +618%) and choline (+148% and +120%), in 19AL and 19 CR rats, respectively. However, brain metabolites did not differ between the 19AL and 19CR groups. Cortex fatty acid profiles showed that n-3 PUFA were 35–47% lower but monounsaturated fatty acids were 40–52% higher in 19AL and 19CR rats compared to 2AL rats. Brain microvessel glucose transporter (GLUT1) was 68% higher in 19AL rats than in 2AL rats, while the monocarboxylate transporter, MCT1, was 61% lower in 19CR rats compared to 19AL rats. We conclude that on a high-sucrose, low n-3 PUFA diet, the brain of aged AL rats had higher metabolites and microvessel GLUT1 expression compared to 2AL rats. However, long-term CR in aged rats did not markedly change brain metabolite or fatty acid profile, but did reduce brain microvessel MCT1 expression.     

A convenient synthesis of lubeluzole and its enantiomer: Evaluation as chemosensitizing agents on human ovarian adenocarcinoma and lung carcinoma cells

Lubeluzole, a neuroprotective anti-ischemic drug, and its enantiomer were prepared following a convenient procedure based on hydrolytic kinetic resolution. The ee values were >99% and 96%, respectively, as assessed by HPLC analysis. The chemosensitizing effects of both enantiomers were evaluated in combination with either doxorubicin (human ovarian adenocarcinoma A2780 cells) or paclitaxel (human lung carcinoma A549 cells) by the MTT assay. At the lowest concentrations used, lubeluzole showed an overall and remarkable tendency to synergize with both anticancer drugs. In ovarian cancer cells a clear prevalence of antagonistic effect was observed for the R-enantiomer. The synergistic effects of lubeluzole for both drugs were observed over a wide concentration window (0.005–5 μM), the lowest limit being at least 40 times lower than human plasma concentrations previously reported as causing serious side effects.     

Chiral discrimination and interaction mechanism between enantiomers and serum albumins

The chiral discrimination studies of biological system are theoretically and practically significant for the development of chiral drugs and life science. Our work has embarked upon the interaction between serum albumin (SA) (including human SA and bovine SA), R,S‐1‐(4‐methoxyphenyl)ethylamine, and R,S‐1‐(3‐methoxyphenyl)ethylamine. The formation of intermediate transition state, binding sites, and chiral discrimination ability can be investigated by ultraviolet‐visible spectra and fluorescence spectra. Moreover, both the changes of hydrophobic microenvironment and energy transfer can be detected by synchronous fluorescence spectra and fluorescence lifetime. Copyright © 2013 John Wiley & Sons, Ltd.     

Preparation of Single-Enantiomer Biofunctional Molecules with (S)-2-Methoxy-2-(1-naphthyl)propanoic Acid

(RS)-β-Ionol and (RS)-2-methyl-4-octanol were resolved by using (S)-2-methoxy-2-(1-naphthyl)propanoic acid [(S)-MαNP acid]. The specific stereochemistry of each MαNP ester was elucidated by 2D NMR analyses, and shielding by the 1-naphthyl group was observed in both the ¹H- and ¹³C-NMR spectra. Solvolysis of the individual (S)-MαNP esters gave four single-enantiomer alcohols. The normal-phase HPLC elution order of each MαNP ester is also discussed.     

Nitrogen Fixation and Allantoin Formation in Soybean Plants

The activity of nitrogenase and the concentration of ammonia and allantoin (+ allantoic acid) in root nodules were measured throughout the growth period of soybean plants. Nitrogenase activity measured by acetylene reduction increased with plant growth and reached a maximum level at the flowering period. The level of ammonia and allantoin concentration in nodules was parallel with increased nitrogenase activity. At the late reproductive stage (pod-forming period), nitrogenase activity showed a marked decrease, but the ammonia and allantoin in the nodules remained at a constant level. Detached nodules from 56 day-old soybean plants were exposed to ¹⁵N₂ gas, and the distribution of ¹⁵N among nitrogen compounds was investigated. Enrichment of ¹⁵N in allantoin and allantoic acid reached a fairly high level after 90 min of nitrogen fixation; ca. 22% of ¹⁵N in acid-soluble nitrogen compounds was incorporated into allantoin + allantoic acid. In contrast, enrichment of ¹⁵N in amide nitrogen was relatively low. No significant ¹⁵N was detected in the RNA fraction. The data suggested that ureide formation in nitrogen-fixing root nodules did not take place through the breakdown of nucleic acids, but directly associated with the assimilating system of biologically fixed nitrogen.     

Metabolically driven equilibrium shift of asymmetric amination of ketones by ω-transaminase using alanine as an amino donor

Removal of a side product to overcome unfavorable equilibrium is a prerequisite for the asymmetric amination of ketones using ω-transaminase (ω-TA). Alanine has been preferred as an amino donor because its deamination product (i.e. pyruvate) is easily removable by several enzymatic methods. Here, we demonstrated that the removal of pyruvate by an innate metabolic pathway could afford equilibrium shift of the ω-TA reactions.     

Estimation of the diversity between DNA calorimetric profiles,differential melting curves and corresponding melting temperatures

The Poland–Fixman–Freire formalism was adapted for modeling of calorimetric DNA melting profiles, and applied to plasmid pBR 322 and long random sequences. We studied the influence of the difference (H_GC?H_AT) between the helix‐coil transition enthalpies of AT and GC base pairs on the calorimetric melting profile and on normalized calorimetric melting profile. A strong alteration of DNA calorimetrical profile with H_GC?H_AT was demonstrated. In contrast, there is a relatively slight change in the normalized profiles and in corresponding ordinary (optical) normalized differential melting curves (DMCs). For fixed H_GC?H_AT, the average relative deviation (S) between DMC and normalized calorimetric profile, and the difference between their melting temperatures (T_cal?T_m) are weakly dependent on peculiarities of the multipeak fine structure of DMCs. At the same time, both the deviation S and difference (T_cal?T_m) enlarge with the temperature melting range of the helix‐coil transition. It is shown that the local deviation between DMC and normalized calorimetric profile increases in regions of narrow peaks distant from the melting temperature.     

A multi‐resolution model to capture both global fluctuations of an enzyme and molecular recognition in the ligand‐binding site

In multi‐resolution simulations, different system components are simultaneously modeled at different levels of resolution, these being smoothly coupled together. In the case of enzyme systems, computationally expensive atomistic detail is needed in the active site to capture the chemistry of ligand binding. Global properties of the rest of the protein also play an essential role, determining the structure and fluctuations of the binding site; however, these can be modeled on a coarser level. Similarly, in the most computationally efficient scheme only the solvent hydrating the active site requires atomistic detail. We present a methodology to couple atomistic and coarse‐grained protein models, while solvating the atomistic part of the protein in atomistic water. This allows a free choice of which protein and solvent degrees of freedom to include atomistically. This multi‐resolution methodology can successfully model stable ligand binding, and we further confirm its validity by exploring the reproduction of system properties relevant to enzymatic function. In addition to a computational speedup, such an approach can allow the identification of the essential degrees of freedom playing a role in a given process, potentially yielding new insights into biomolecular function. Proteins 2016; 84:1902–1913. © 2016 Wiley Periodicals, Inc.     

Intense Chiral Optical Phenomena in Racemic Polymers by Cocrystallization With Chiral Guest Molecules: A Brief Overview

This review is devoted to the chiral optical behavior of films of racemic polymers whose chirality is induced by cocrystallization with nonracemic (also temporary) guest molecules. We provide examples of macromolecular amplification of chirality, produced by molecular and supramolecular mechanisms, on industrially relevant polymers like poly(2,6‐dimethyl‐1,4‐phenylene)oxide (PPO) and syndiotactic polystyrene (s‐PS). Chirality 28:29–38, 2016. © 2015 Wiley Periodicals, Inc.