Remote Positions Research Articles

Remote Participation of Protecting Groups at Remote Positions of Donors in Glycosylations

Effects of potentially participating groups at remote positions of glycopyranosyl and glycofuranosyl donors on the glycosylation stereochemistry are reviewed. Substantial evidences in favor of the remote participation by protecting groups are presented and also included are a few reports opposed to the remote participation.

Applications of remote stereocontrol using allylstannanes: an approach to the stereoselective synthesis of aliphatic polyols

(4 R,2 E)-4-Benzyloxy-octa-2,7-dienyl(tributyl)stannane was transmetalated by tin(IV) chloride to generate an allyltin trichloride, which reacted with aldehydes to give (3 Z)-1,5- syn-5-benzyloxynona-3,8-dien-1-ols with useful 1,5-stereocontrol. O-Benzylation, hydroboration and oxidation of the terminal double-bond of the product from 2-methylpropanal gave (5 R,9S,6 Z)-5,9-dibenzyloxy-10-methylundec-6-enal. Further reactions with 4-alkoxyalk-2-enylstannanes proceeded with useful 1,5-stereocontrol to give open-chain products with hydroxy or benzyloxy substituents stereoselectively disposed at remote positions along the chain.

Shadow Enhancers Foster Robustness of Drosophila Gastrulation

Critical developmental control genes sometimes contain "shadow" enhancers that can be located in remote positions, including the introns of neighboring genes [1]. They nonetheless produce patterns of gene expression that are the same as or similar to those produced by more proximal primary enhancers. It was suggested that shadow enhancers help foster robustness in gene expression in response to environmental or genetic perturbations [2, 3]. We critically tested this hypothesis by employing a combination of bacterial artificial chromosome (BAC) recombineering and quantitative confocal imaging methods [2, 4]. Evidence is presented that the snail gene is regulated by a distal shadow enhancer located within a neighboring locus. Removal of the proximal primary enhancer does not significantly perturb snail function, including the repression of neurogenic genes and formation of the ventral furrow during gastrulation at normal temperatures. However, at elevated temperatures, there is sporadic loss of snail expression and coincident disruptions in gastrulation. Similar defects are observed at normal temperatures upon reductions in the levels of Dorsal, a key activator of snail expression (reviewed in [5]). These results suggest that shadow enhancers represent a novel mechanism of canalization whereby complex developmental processes "bring about one definite end-result regardless of minor variations in conditions" [6].

Phenotypic robustness conferred by apparently redundant transcriptional enhancers

Genes include cis-regulatory regions that contain transcriptional enhancers. Recent reports have shown that developmental genes often possess multiple discrete enhancer modules that drive transcription in similar spatio-temporal patterns1-4: primary enhancers located near the basal promoter and secondary, or “shadow”, enhancers located at more remote positions. It has been hypothesized that the seemingly redundant activity of primary and secondary enhancers contributes to phenotypic robustness1,5. We tested this hypothesis by generating a deficiency that removes two newly-discovered enhancers of shavenbaby (svb), a gene encoding a transcription factor that directs development of larval trichomes6. At optimal temperatures for embryonic development, this deficiency causes minor defects in trichome patterning. In embryos that develop at both low and high extreme temperatures, however, absence of these secondary enhancers leads to extensive loss of trichomes. These temperature-dependent defects can be rescued by a transgene carrying a secondary enhancer driving transcription of the svb cDNA. Finally, removal of one copy of wingless, a gene required for normal trichome patterning7, causes a similar loss of trichomes only in flies lacking the secondary enhancers. These results support the hypothesis that secondary enhancers contribute to phenotypic robustness in the face of environmental and genetic variability.

10.1007/s11173-008-2004-x

The products of oxidation of ethylenediaminetetraacetic acid by manganese dioxide have been used to synthesize crystals of [Cu(Edda)(Phen)] · 5H2O (Edda is ethylenediamine-N,N′-diacetate, and Phen is 1,10-phenanthroline). The X-ray diffraction analysis of the crystals shows that the N atoms of the Edda and Phen ligands lie in the equatorial plane around the Cu atom, and the O atoms of the Edda ligands are localized in more remote axial positions. The [Cu(Edda)(Phen)] complexes are grouped in pairs at a distance of 3.46 Å between the mean planes of the Phen ligands. Ten water molecules are united by hydrogen bonds into symmetric isolated clusters, and further they form a three-dimensional framework with the [Cu(Edda)(Phen)] complexes.

Microbial Transformation of Triterpenoids

Microbial transformation of triterpenoids has provided new derivatives that are potentially useful for pharmacological studies. In these biotransformation processes, several reactions that are difficult to achieve by chemical means have been accomplished, such as: introduction of hydroxyl groups into remote positions of the molecules; selective cleavage of the side chains of tetra-cyclic terpenoids to produce C19 steroids; regioselective glycosidic transfer reactions; selective ring cleavage through a Baeyer-Villiger-type oxidation to render seco-triterpenoids; and carbon skeleton rearrangements involving a methyl group migration. These biotransformations have also been used as in vitro models to mimic and predict the mammalian metabolism of biologically active triterpenoids. Keywords: Microbial transformation, biotransformation, triterpenoid, triterpene, filamentous fungi, bacteria

Biotransformation of Terpenoids: A Green Alternative for Producing Molecules with Pharmacological Activity

Terpenoids are natural products of great interest due to their broad application scope. They are employed as agrochemicals, drugs, fragrances, flavours and pigments. In the search of new derivatives with improved properties, the use of biocatalysts is being constantly increased, especially in redox processes. They can give rise to stereo- and regioselective products and/or compounds functionalized in remote positions difficult to reach by means of traditional organic chemistry. In this review, the application of whole cell catalyzed biotransformations of terpenoids to obtain new drug targets or to increase the pharmacological activity is presented. Keywords: Terpenes, terpenoids, biotransformations, enzymes, redox process

Occupational therapy practice in rural and remote South Australia

Health care delivery in rural and remote areas of Australia is a challenge because of the distances involved together with the sparse population cover. In this issue, health care delivery in rural and remote South Australia is tackled from the perspective of occupational therapy managers. Boshoff and Hartshorne1 describe the services provided by occupational therapists as well as the strategies employed by therapists to deliver services. They used surveys to gather the data. Survey data can provide a description of the ‘state of play’. What the Boshoff and Hartshorne article gives, together with other knowledge that is accumulating on the allied health professions in rural and remote areas,2 is a description of what is happening ‘on the ground’. Having worked as a therapist in a multidisciplinary team covering a large rural area with a high client–therapist caseload, the findings of this study raised issues I could identify with, for example, the variety of work and community settings used by therapists to deliver services. In order to deliver services across wide geographical areas, rural and remote therapists require in-depth knowledge of their community and the resources (both people and places) within that community. The professional knowledge of health professionals needed to service clients varies little between metropolitan and rural and remote areas. The challenge to health professionals outside metropolitan areas is the tension between specialist versus generalist knowledge and how to deliver services over vast areas. Mills and Millsteed3 described the knowledge used by occupational therapists in rural and remote areas as more generalist than specialist. Rural and remote therapists work over wide geographical regions, which results in the provision of services to a wide age range of people with a wide range of health conditions. This makes developing highly refined specialised knowledge of certain conditions or of population groups difficult, and this situation was identified by the South Australian occupational therapists. Boshoff and Hartshorne found that the knowledge base of occupational therapy worked well in rural areas because of its holistic, problem-solving stance, and this combined with other strategies, such as multiskilling of therapists and continuing professional development, were used to cope with the need for such a wide knowledge base. Health services in rural and remote areas cannot be provided without staff on the ground. Retention of rural and remote staff is an issue that is receiving more and more attention as service providers and governments seek information on what factors influence staff to stay or leave positions.2, 4 Maintaining health professionals ‘on the ground’ is a complex interplay between professional and personal needs. Boshoff and Hartshorne described a workforce where just over half of the respondents had 2 years or less of experience in a rural area. In Queensland, rural areas have been called ‘professional nurseries’5 with new graduates making up large proportions of the workforce. Retaining young professionals in rural and remote positions is a challenge. The Boshoff and Hartshorne study made the interesting finding that the vast majority of therapists felt adequately supported in the work place even though they were working with high client–therapist caseloads and covering large geographical regions. Support has been found to be an important indicator of retention in other studies.3, 6 A variety of strategies were used to provide a sense of support for therapists, such as student networks, networking, professional associations and communication (by various means) within the profession and across professions, local and regional meetings, continuing professional development and exchange of information and knowledge with therapists in metropolitan areas. Support of managers, other therapists, support from other disciplines, support for further training and up-skilling and support of allied health support staff were important to maintaining a sense of connection to the profession, the field and an increase in knowledge. Good networking reduces the sense of isolation and gives the feeling of being in a dynamic learning environment. Networking and networks are important to rural and remote therapists. Heath services that recognise the time and importance of networking and building up networks are organisations that support staff because networks assist in problem solving, can be a means to providing a variety of services, and also provide another level of social interaction for the therapist within the community. Allied health professionals provide important health services in primary, secondary and tertiary areas of health care. Maintaining a highly qualified and stable allied health service in rural and remote areas of Australia is important for Australians' health and well-being.

Self-selection in the self-assembly of isomeric supramolecular squares from unsymmetrical bis(4-pyridyl)acetylene ligands.

A new approach wherein steric interactions between substituents of unsymmetrical bis(4-pyridyl)acetylene ligands dictate the self-selection of single isomers of [4 + 4] self-assembled squares is presented. Each [4 + 4] self-assembly is characterized by multinuclear (31)P and (1)H NMR spectroscopies and electrospray ionization mass spectrometry. NMR spectroscopic studies are used to provide a means of evaluating the efficiency of bulky substituents at proximal or remote positions relative to the Pt-N bonding motif to direct self-selection. Molecular modeling using the MMFF force field is utilized to determine the relative energy of different isomers of each assembly, and modeling results reasonably explain the trend in self-selectivity with varying pyridyl substitution.

A fluorescent linear optical fiber position sensor

This paper describes a fluorescent long-line optical fiber position sensor to satisfy an industrial need for measuring position over a wide range of distances, varying from centimeters to many meters, where high resolution is not required. As is well-known, the light power transmitted by an optical fiber decreases with distance. By measuring the light power collected at both ends of a fluorescent long-line optical fiber, a position sensor has been developed. The position of the point where a light beam enters the fiber can be determined by comparing the light power collected at its two ends. In addition to their low cost and easiness of handling, plastic optical fibers present the advantages common to all multimode optical fibers such as flexibility, small size, and a good behaviour against electromagnetic interferences. Besides, sensors based on optical fiber eliminate the risk of electrical sparks in explosive environments, and they can be read from remote positions. In this work, several fluorescent optical fibers with different diameters, wavelengths, and light sources have been tested.

Measurement of equal-loudness contours using eardrum pressure as reference signal

Equal-loudness contours represent the relationship of loudness perception and sound pressure at the ear. Usually, the reference pressure is defined with a standardised calibration procedure. Individual ear canal characteristics significantly influence the contours, resulting in peaks and notches. By choosing the eardrum pressure as reference for the perception measurements, individual ear canal features are cancelled, when loudness and pressure are related. Thus, flatter contours can be achieved. Finite-element simulations of the sound field in the canal have shown that signals at remote positions may differ significantly from the eardrum pressure. Thus, to achieve eardrum related measurements, it is necessary to insert probe microphones sufficiently deep into the canal. However, the desired signal has to be estimated from a distance, since measurements directly at the drum are not practical. A method is shown to determine both the probe tip distance and the transformation terms to calculate the drum pressure estimate. In this contribution, the results of equal-loudness contour measurements are discussed. The positioning and transformation processes are verified by simulations with one-dimensional and finite-element models and experiments.

Characterisation of structure borne sound sources from measurement in-situ

In-situ source characterisation methods are those which involve measurements made whilst source and receiver are coupled as they would be in a real installation. Potentially in-situ source characterisation may account for the physical reality lost in the "black box" approach. There are other potential benefits such as ease of measurement. In this work a structure borne sound source is characterised using in-situ measurements of blocked force and coupled mobility. Promising results from the method have been presented previously. Further to this, an extension of the method allowing the use remote measurement positions has been developed. Using reciprocity, the extended method will further ease measurement for situations where access poses a problem. The extended method is outlined and some preliminary validation results are presented.

Crystal structure of (1,10-phenanthroline)ethylenediamine-N,N′-diacetatocopper(II) pentahydrate, [Cu(Edda)(Phen)] · 5H2O

The products of oxidation of ethylenediaminetetraacetic acid by manganese dioxide have been used to synthesize crystals of [Cu(Edda)(Phen)] · 5H2O (Edda is ethylenediamine-N,N′-diacetate, and Phen is 1,10-phenanthroline). The X-ray diffraction analysis of the crystals shows that the N atoms of the Edda and Phen ligands lie in the equatorial plane around the Cu atom, and the O atoms of the Edda ligands are localized in more remote axial positions. The [Cu(Edda)(Phen)] complexes are grouped in pairs at a distance of 3.46 A between the mean planes of the Phen ligands. Ten water molecules are united by hydrogen bonds into symmetric isolated clusters, and further they form a three-dimensional framework with the [Cu(Edda)(Phen)] complexes.

Stereocontrolled Construction of Seven-Membered Carbocycles Using a Combination of Brook Rearrangement-Mediated [3 + 4] Annulation and Epoxysilane Rearrangement

Reactions of delta-silyl-gamma,delta-epoxy-alpha,beta-unsaturated acylsilane with alkenyl methyl ketone enolate afford highly functionalized cycloheptenone derivatives via a tandem sequence featuring the combination of Brook rearrangement-mediated [3 + 4] annulation and epoxysilane rearrangement. The reactions using an opposite combination of three and four carbon units, in which an epoxysilane moiety was incorporated in the four-carbon unit, also give satisfactory results. Also, the possibility of chirality transfer from epoxide to remote positions via the tandem sequence using an optically active epoxide has been demonstrated.

Adsorption of benzene from an aqueous solution

Adsorption of benzene from aqueous solution on a planar carbon wall is studied by molecular dynamics simulations. The density profile and the orientational behavior of a benzene molecule are determined by two methods. In the first one the center of the benzene molecule is fixed while the molecule can freely rotate and the local density is obtained via integration of the mean force on the center of the molecule. In the second method the density profile is determined directly from a freely moving benzene molecule. It turns out that even in the case of strong adsorption the first method is superior. As regards structure, the benzene molecule is preferably adsorbed in a nearly parallel orientation to the wall, but there is also a certain probability for finding it in more remote positions in an almost perpendicular orientation bridging two water layers.

DNA looping induced by a transcriptional enhancer in vivo

Enhancers are DNA sequences that can activate gene transcription from remote positions. In yeast, regulatory sequences that are functionally equivalent to the metazoan enhancers are called upstream activating sequences (UASs). UASs show a lower degree of flexibility than their metazoan counterparts, but can nevertheless activate transcription from a distance of >1000 bp from the promoter. One of several models for the mechanism of action of transcriptional enhancers proposes that enhancer-bound activating proteins contact promoter-bound transcription factors and thereby get in close proximity to the promoter region with concomitant looping of the intervening DNA. We tested the mode of enhancer activity in yeast. A polymerase II-transcribed gene was paired with a remote, inducible enhancer. An independent reporter system was inserted next to the promoter to monitor the potential modes of enhancer activity. Our results show that the enhancer activated the reporter system only in the presence of a functional promoter. We also demonstrate that the heterologous expression of GAGA, a factor known to facilitate DNA loop formation, allows enhancer action in yeast over a distance of 3000 bp.

Reactions of hydroxylated sodium nitronates with acetic anhydride/pyridine

Reactions with Ac 2O/Py of sodium nitronate salts derived from primary or secondary nitroalkanes bearing hydroxyl groups at γ or more remote positions have been studied. In all cases, the results could be explained through an acetic nitronic anhydride intermediate, whose evolution depends on conformational factors, and also on the type of the hydroxyl group.

Removing a hydrogen bond in the dimer interface of Escherichia coli manganese superoxide dismutase alters structure and reactivity.

Among manganese superoxide dismutases, residues His30 and Tyr174 are highly conserved, forming part of the substrate access funnel in the active site. These two residues are structurally linked by a strong hydrogen bond between His30 NE2 from one subunit and Tyr174 OH from the other subunit of the dimer, forming an important element that bridges the dimer interface. Mutation of either His30 or Tyr174 in Escherichia coli MnSOD reduces the superoxide dismutase activity to 30--40% of that of the wt enzyme, which is surprising, since Y174 is quite remote from the active site metal center. The 2.2 A resolution X-ray structure of H30A-MnSOD shows that removing the Tyr174-->His30 hydrogen bond from the acceptor side results in a significant displacement of the main-chain segment containing the Y174 residue, with local rearrangement of the protein. The 1.35 A resolution structure of Y174F-MnSOD shows that disruption of the same hydrogen bond from the donor side has much greater consequences, with reorientation of F174 having a domino effect on the neighboring residues, resulting in a major rearrangement of the dimer interface and flipping of the His30 ring. Spectroscopic studies on H30A, H30N, and Y174F mutants show that (like the previously characterized Y34F mutant of E. coli MnSOD) all lack the high pH transition of the wt enzyme. This observation supports assignment of the pH sensitivity of MnSOD to coordination of hydroxide ion at high pH rather than to ionization of the phenolic group of Y34. Thus, mutations near the active site, as in the Y34F mutant, as well as at remote positions, as in Y174F, similarly affect the metal reactivity and alter the effective pK(a) for hydroxide ion binding. These results imply that hydrogen bonding of the H30 imidazole N--H group plays a key role in substrate binding and catalysis.

Transcriptional Repression Mediated by the KRAB Domain of the Human C2H2 Zinc Finger Protein Kox1/ZNF10 Does Not Require Histone Deacetylation

The KRAB domain of human Kox1, a member of the KRAB C2H2 zinc finger family, confers strong transcriptional repressor activities even to remote promoter positions. Here, HDAC inhibitors were used to demonstrate that histone deacetylation is not required for mediating transcriptional repression of KRAB zinc finger proteins. Two reporter systems with either stably integrated or transiently transfected templates, both under control of strong viral promoters, were analyzed. Under all circumstances, HDAC inhibition did not alter the repression potential of the KRAB domain. In case of the stably integrated luciferase reporter gene system, neither expression levels of the KRAB fusion protein nor complex formation with its putative co-repressor TIF1beta were significantly changed. Furthermore, the TIF1beta/KRAB complex was devoid of mSin3A and HDAC1. In the transient transfection system, the transcriptional repression induced by TIF1beta and HP1alpha was not diminished by HDAC inhibitors, whereas the repressory activity of TIF1alpha was significantly affected. Thus, KRAB, TIF1beta and HP1alpha are likely to be functionally linked. In conclusion, HDAC activity is not essential for the strong transcriptional repressor activity mediated by the KRAB domain of Kox1 in particular and, presumably, by KRAB domains in general. This feature might be helpful in identifying and characterizing target genes under the control of

Effect of substitution pattern on 1H, 13C NMR chemical shifts and 1JCH coupling constants in heparin derivatives

1H, 13C NMR chemical shifts and 1 J CH coupling constants were measured for derivatives of heparin containing various sulfation patterns. 1H and 13C chemical shifts varied considerably after introducing electronegative sulfate groups. Chemical shifts of protons linked to carbons changed by up to 1 ppm on substitution with O- and N-sulfate or acetyl groups. Differences up to 10 ppm were detected for 13C chemical shifts in substituted glucosamine, but a less clear dependence was found in iduronate. 1 J CH values formed two groups, corresponding to either sulfation or non-sulfation at positions 2 and 3 of glucosamine. O-sulfation caused increases up to 6 Hz in 1 J CH and N-sulfation decreases up to 4 Hz. N-acetylation gave similar 1 J CH values to N-sulfation. At positions 2 and 3 of iduronate the trend was less marked; 1 J CH for O-sulfated positions usually increasing. Introduction of sulfate groups influences chemical shift and 1 J CH values at the position of substitution, but also at more remote positions. 1 J CH at the glycosidic linkage positions varied between free-amino and N-sulfated compounds, by up to 9 Hz. These results and changes in chemical shift values suggest that iduronate residues and the glycosidic linkages are affected, indicating overall conformational change. This may have important implications for biological activities.