Stereoselective HDAC Inhibition from Cysteine‐Derived Zinc‐Binding Groups

A series of small‐molecule histone deacetylase (HDAC) inhibitors, which feature zinc binding groups derived from cysteine, were synthesized. These inhibitors were tested against multiple HDAC isoforms, and the most potent, compound 10 , was determined to have IC₅₀ values below 1 μM . The compounds were also tested in a cellular assay of oxidative stress‐induced neurodegeneration. Many of the inhibitors gave near‐complete protection against cell death at 10 μM without the neurotoxicity seen with hydroxamic acid‐based inhibitors, and were far more neuroprotective than HDAC inhibitors currently in clinical trials. Both enantiomers of cysteine were used in the synthesis of a variety of novel zinc‐binding groups (ZBGs). Derivatives of L ‐cysteine were active in the HDAC inhibition assays, while the derivatives of D ‐cysteine were inactive. Notably, the finding that both the D ‐ and L ‐cysteine derivatives were active in the neuroprotection assays suggests that multiple mechanisms are working to protect the neurons from cell death. Molecular modeling was employed to investigate the differences in inhibitory activity between the HDAC inhibitors generated from the two enantiomeric forms of cysteine.     

Optimal environmental search and scattered orientations during movement of adult rusty grain beetles, Cryptolestes ferrugineus (Stephens), in grain bulks – suggested movement and distribution patterns

An understanding of insect movement and distribution within grain bulks is essential to effectively control insect pests. In this paper, opinions published in the literature and related to random, downward, and bias movements (the tendency to move in non-random directions) of adults of Cryptolestes ferrugineus have been compared and the net displacement of C. ferrugineus adults in stored-grain bulks was calculated. The average net displacement of the adults inside a stored-wheat mass was 0.435 ± 0.229 m/d. The causes of the scattered orientations were analyzed and the following points were suggested: 1) both experimental observations and theoretical analyses did not support the view that adults of C. ferrugineus exhibit a positive geotactic behavior; 2) the downward movement might be caused by adults' drifting; 3) during their bias movements in responding to environmental factors such as temperature gradients, adults did not significantly decrease their random movements; and 4) their dispersal inside granaries might be mainly influenced by their random movement, drift, and scattered orientations. At the individual level, they were always moving toward optimal environmental areas. At the population level, the random movement plus scattered orientations resulted in a diffusion distribution pattern. Comparison between the suggested diffusion pattern and the insect distributions published in the literature in the following areas was conducted: theoretical analyses of insect diffusion, movements and distributions under laboratory conditions, and dispersal in full-size granaries. Results show that the published insect distributions were consistent with the suggested diffusion pattern.     

From 5-Hydroxymethylfurfural (HMF) to Polymer Precursors: Catalyst Screening Studies on the Conversion of 1,2,6-hexanetriol to 1,6-hexanediol

1,6-hexanediol (1) is an important polymer precursor for the polyester industry. In this paper, exploratory catalyst screening studies on the synthesis of 1 from 1,2,6-hexanetriol (2) are described via two different routes. The latter is available by a two-step procedure from 5-hydroxymethylfurfural (HMF, 3), a promising bio-based platform chemical. In the first approach, the direct catalytic hydrodeoxygenation of 2 to 1 with heterogeneous catalysts and molecular hydrogen was explored. Best results were obtained using a Rh?CReO_x/SiO₂ catalyst in water (180?°C, 80?bar H₂, 20?h reaction time), leading to full conversion of 2 and 73?% selectivity to 1, the main byproduct being 1,5-hexanediol (4). In a second approach, 2 was first converted to tetrahydropyran-2-methanol (2-THPM, 5) in quantitative yield using triflic acid as catalyst (125?°C, 30?min). Various catalysts were explored for the subsequent ring opening/hydrodeoxygenation of 5 to 1 using a hydrogenation protocol and the best results were obtained with a Rh?CReO_x/SiO₂ catalyst, viz. 96?% selectivity to 1 at 26?% conversion (120?°C, 80?bar H₂, 20?h).     

Stability of Plant Defensive Traits Among Populations in Two Eucalyptus Species Under Elevated Carbon Dioxide

Plant secondary metabolites (PSMs) mediate a wide range of ecological interactions. Investigating the effect of environment on PSM production is important for our understanding of how plants will adapt to large scale environmental change, and the extended effects on communities and ecosystems. We explored the production of PSMs under elevated atmospheric carbon dioxide ([CO₂]) in the species rich, ecologically and commercially important genus Eucalyptus. Seedlings from multiple Eucalyptus globulus and E. pauciflora populations were grown in common glasshouse gardens under elevated or ambient [CO₂]. Variation in primary and secondary chemistry was determined as a function of genotype and treatment. There were clear population differences in PSM expression in each species. Elevated [CO₂] did not affect concentrations of individual PSMs, total phenolics, condensed tannins or the total oil yield, and there was no population by [CO₂] treatment interaction for any traits. Multivariate analysis revealed similar results with significant variation in concentrations of E. pauciflora oil components between populations. A [CO₂] treatment effect was detected within populations but no interactions were found between elevated [CO₂] and population. These eucalypt seedlings appear to be largely unresponsive to elevated [CO₂], indicating stronger genetic than environmental (elevated [CO₂]) control of expression of PSMs.     

Corneal changes following short-term rigid contact lens wear

PurposeThe aim of this cross-over study was to investigate the changes in corneal thickness, anterior and posterior corneal topography, corneal refractive power and ocular wavefront aberrations, following the short term use of rigid contact lenses.MethodFourteen participants wore 4 different types of contact lenses (RGP lenses of 9.5 mm and 10.5 mm diameter, and for comparison a PMMA lens of 9.5 mm diameter and a soft silicone hydrogel lens) on 4 different days for a period of 8 h on each day. Measures were collected before and after contact lens wear and additionally on a baseline day.ResultsAnterior corneal curvature generally showed a flattening with both of the RGP lenses and a steepening with the PMMA lens. A significant negative correlation was found between the change in corneal swelling and central and peripheral posterior corneal curvature (all p ≤ 0.001). RGP contact lenses caused a significant decrease in corneal refractive power (hyperopic shift) of approximately 0.5 D. The PMMA contact lenses caused the greatest corneal swelling in both the central (27.92 ± 15.49 μm, p < 0.001) and peripheral (17.78 ± 12.11 μm, p = 0.001) corneal regions, a significant flattening of the posterior cornea and an increase in ocular aberrations (all p ≤ 0.05).ConclusionThe corneal swelling associated with RGP lenses was relatively minor, but there was slight central corneal flattening and a clinically significant hyperopic change in corneal refractive power after the first day of lens wear. The PMMA contact lenses resulted in significant corneal swelling and reduced optical performance of the cornea.     

A quantitative comparison of phytochemical components in global noni fruits and their commercial products

The fruits of noni (Morinda citrifolia L.) have been used as a medicinal food for centuries in a wide range of tropical regions, and are increasingly attracting more attention worldwide. Due to the increase of commercial noni fruit products in the global market, an extensive phytochemical comparison of noni fruits and their juice products seems imperative to understand their internal quality. To this end, we developed an HPLC method, established phytochemical fingerprints, and quantitatively compared the characteristic components in 7 noni fruits and 13 commercial fruit juices originating from the Caribbean, Central America, the Central and South Pacific, and Asia. The results showed that scopoletin, rutin, quercetin, and 5,15-dimethylmorindol were detected in all the samples, although at varying concentrations. Together, these components could be used as a reference for identification and authentication of raw noni fruits and their commercial products. Meanwhile, the variation in phytochemical content in noni fruits and juices may be attributed to the diversity of geographical environments (soil, sunlight, temperature, precipitation, etc.) and post-growth factors (harvesting, storage, transportation, manufacturing processes, formulation, etc.). Further, the variation may also suggest different toxicological and pharmacological profiles. As such, scientific data of efficacy and safety conducted on one noni fruit or juice may not be applicable to all others, including those from the same origins.     

Indium tin oxide nanowhisker morphology control by vapour-liquid-solid glancing angle deposition

A new growth technique for indium tin oxide nanowhiskers with increased control over feature size and spacing is reported. The technique is based on a unique combination of self-catalysed vapour-liquid-solid (VLS) growth and glancing angle deposition (GLAD). This VLS-GLAD technique provides enhanced control over nanowhisker morphology as the effect of typical VLS growth parameters (e.g.?flux rate, temperature) is amplified at large deposition angles characteristic of GLAD. Spatial modulation of the collimated growth flux controls trunk width, number and orientation of branches, and overall nanowhisker density. Here we report the influence of growth conditions (including deposition angle, flux rate, nominal pitch and substrate temperature) on nanowhisker morphology, with specific focus on the effect of large deposition angles. Sheet resistance and transmission of the films were measured to characterize their performance as transparent conductive oxides. Hybrid nanostructured films grown in this study include high surface area nanowhiskers protruding from a conductive film, ideal for transparent conductive electrode applications.     

Thorough empirical analysis of the IETF FMIPv6 protocol over IEEE 802.11 networks [architectures and protocols for mobility management in all-IP mobile networks]

The development of network technologies such as wireless LAN have made it possible for users to benefit from Internet connectivity almost anywhere and at anytime. In order to improve user experience, the IETF has defined the Mobile IPv6 protocol which allows mobile nodes to maintain their communication uninterrupted while roaming across various IPv6 subnets. However, the mechanisms this protocol defines may cause undesired connection disruption and/or substantial packet loss which may significantly degrade the quality of real-time media streams. To address the problems of handover latency, the Mipshop IETF working group has adopted and developed the FMIPv6 protocol. Previous analysis, including some of our own, has shown that the protocol is particularly efficient in reducing both the duration of handovers and the number of lost packets. However, these previous works are often based on theoretical studies and simulations, or do not analyze all FMIPv6 operations and features. We therefore present in this article a thorough experimental evaluation of FMIPv6 over wireless LANs. This article extends our previous work by evaluating all aspects of FMIPv6: predictive handovers, reactive handovers, and network-initiated handovers. We also evaluate the benefits of FMIPv6 on layer 2 only handovers. All experiments are conducted with unmodified versions of the popular conferencing and video streaming applications Gnomemeeting and VLC.     

The Effect of Additives on Amorphous Calcium Carbonate (ACC): Janus Behavior in Solution and the Solid State

Amorphous calcium carbonate (ACC) is an important intermediate in the formation of crystalline CaCO₃ biominerals, where its crystallization is controlled using soluble additives. However, although this transformation often occurs in the solid state, experiments mainly focus on the effect of additives on ACC crystallization in solution. This paper addresses this issue and compares the crystallization, in solution and in the solid state, of ACC precipitated in the presence of a range of additives. Surprisingly, these results show that some additives exhibit a Janus behavior, where they retard crystallization in solution, yet accelerate it in the solid state. This is observed for all of the larger molecules examined, while the small molecules retard crystallization in both solution and the solid state.