A biocatalytic resolution of chiral ketals, intermediates in the synthesis of azole drugs

Crude lipases are used for the resolution of racemic ketals advanced intermediates in the synthesis of cis-terconazole and cis-ketoconazole. Lipase from Aspergillus niger allows to obtain the (2R, 4R)-enantiomer of the imidazole-substituted ketal in good ee at low conversion. The addition of adsorbing resins improves the efficiency to interesting ee values for practical applications. The compound is transformed into (2R, 4S)-terconazole. The survived ester gives access to the other enantiomer.     

Screening and catalytic activity in organic synthesis of novel fungal and yeast lipases

A total of 969 microbial strains were isolated from soil samples and tested to determine their lipolytic activity by employing screening techniques on solid and in liquid media. Ten lipase-producing microorganisms were selected and their taxonomic identification was carried out. From these strains Achremonium murorum, Monascus mucoroides, Arthroderma ciferri, Fusarium poae, Ovadendron sulphureo-ochraceum and Rhodotorula araucariae are described as lipase-producers for the first time. Hydrolysis activity of the crude lipases against both tributyrin and olive oil was measured. Heptyl oleate synthesis was carried out to test the activity of the selected lipases as biocatalysts in organic medium. All the selected lipases were tested as biocatalysts in several organic reactions using unnatural substrates. Lipases from the fungi Fusarium. oxysporum and O. sulphureo-ochraceum gave the best yields and enantioselectivities in the esterification of carboxylic acids. F. oxysporum and Penicillium chrysogenum lipases were the most active ones for the acylation of alcohols without steric hindrance. A. murorum lipase is very useful for the esterification of menthol. F. oxysporum and Fusarium. solani lipases were very stereoselective in the synthesis of carbamates.     

Full field spatially-variant image-based resolution modelling reconstruction for the HRRT

Accurate characterisation of the scanner's point spread function across the entire field of view (FOV) is crucial in order to account for spatially dependent factors that degrade the resolution of the reconstructed images. The HRRT users' community resolution modelling reconstruction software includes a shift-invariant resolution kernel, which leads to transaxially non-uniform resolution in the reconstructed images. Unlike previous work to date in this field, this work is the first to model the spatially variant resolution across the entire FOV of the HRRT, which is the highest resolution human brain PET scanner in the world. In this paper we developed a spatially variant image-based resolution modelling reconstruction dedicated to the HRRT, using an experimentally measured shift-variant resolution kernel. Previously, the system response was measured and characterised in detail across the entire FOV of the HRRT, using a printed point source array. The newly developed resolution modelling reconstruction was applied on measured phantom, as well as clinical data and was compared against the HRRT users' community resolution modelling reconstruction, which is currently in use. Results demonstrated improvements both in contrast and resolution recovery, particularly for regions close to the edges of the FOV, with almost uniform resolution recovery across the entire transverse FOV. In addition, because the newly measured resolution kernel is slightly broader with wider tails, compared to the deliberately conservative kernel employed in the HRRT users' community software, the reconstructed images appear to have not only improved contrast recovery (up to 20% for small regions), but also better noise characteristics.     

Creating the conditions for peacemaking: theories of practice in ethnic conflict resolution

Establishing the conditions for effective intergroup peacemaking is a formidable task in severe ethnic conflicts. Conflict resolution practitioners argue that a critical first step is developing preconditions which convince competing groups that there are opponents to whom it is worth talking, that it is possible to create structural changes conducive to a stable peace, and that an agreement is possible which can meet each side's basic concerns and needs. This article compares six theories of practice of ethnic conflict resolution: community relations, principled negotiation; human needs; psychoanalytically rooted identity; intercultural miscommunications and conflict transformation, examining how each understands ethnic conflict; the goals it articulates; the effects of good practice on participants in interventions; the mechanisms by which the project achieves its impact; and the dynamics of transfer affecting the course of a wider conflict. It is argued that clearer articulation of these assumptions will improve both theory and practice in the search for settlements to severe ethnic conflict.     

Paradigm shift – Metabolic transformation of docosahexaenoic and eicosapentaenoic acids to bioactives exemplify the promise of fatty acid drug discovery

Fatty acid drug discovery (FADD) is defined as the identification of novel, specialized bioactive mediators that are derived from fatty acids and have precise pharmacological/therapeutic potential. A number of reports indicate that dietary intake of omega-3 fatty acids and limited intake of omega-6 promotes overall health benefits. In 1929, Burr and Burr indicated the significant role of essential fatty acids for survival and functional health of many organs. In reference to specific dietary benefits of differential omega-3 fatty acids, docosahexaenoic and eicosapentaenoic acids (DHA and EPA) are transformed to monohydroxy, dihydroxy, trihydroxy, and other complex mediators during infection, injury, and exercise to resolve inflammation. The presented FADD approach describes the metabolic transformation of DHA and EPA in response to injury, infection, and exercise to govern uncontrolled inflammation. Metabolic transformation of DHA and EPA into a number of pro-resolving molecules exemplifies a novel, inexpensive approach compared to traditional, expensive drug discovery. DHA and EPA have been recommended for prevention of cardiovascular disease since 1970. Therefore, the FADD approach is relevant to cardiovascular disease and resolution of inflammation in many injury models. Future research demands identification of novel action targets, receptors for biomolecules, mechanism(s), and drug-interactions with resolvins in order to maintain homeostasis.     

Visual acuity, contrast sensitivity and retinal magnification in a marsupial, the tammar wallaby (Macropus eugenii )

The visual acuity of the tammar wallaby was estimated using a behavioural discrimination task. The wallabies were trained to discriminate a high-contrast (86%) square-wave grating from a grey field of equal luminance (1000–6000 cd m⁻²). Visual-evoked cortical potentials were used to measure the complete contrast sensitivity function. The stimulus was a sinusoidal phase reversal of a sinusoidally modulated grating of various spatial frequencies and contrasts with a mean luminance of 40 cd m⁻². The behavioural acuity was estimated to be about 4.8 cycles/deg. The contrast sensitivity peaked at about 0.15 cycles/deg and declined towards both lower and higher spatial frequencies. The cut-off frequency of the contrast sensitivity function is slightly lower than the behaviourally measured acuity at about 2.7 cycles/deg. The retinal magnification factor was estimated anatomically from laser lesions to be about 0.16 mm/deg. Based on the known ganglion cell density and the retinal magnification factor, an anatomical upper limit to visual acuity of about 6 cycles/deg can be calculated. The differences in estimates of visual acuity between the behavioural and anatomical methods on the one side and physiology on the other side are discussed. Accepted: 28 May 1998     

Spontaneous and induced generation of optical activity in racemic 1,1′-Binaphthyl

Summary A racemic mixture of the molecularly dissymmetric compound 1,1-binaphthyl will spontaneously develop optical activity when melted, cooled, and allowed to crystallize. The distribution of optical rotations in individual samples shows that the resolutions occur in a truly spontaneous manner (i.e., without the influence of any external chiral agent). However, addition of small amounts of certain chiral compounds promotes the generation of one enantiomeric form of binaphthyl. The results are often not completely consistent and this suggests that the nucleation of binaphthyl is sensitive to very low concentrations of unknown chiral agents.Presented at the International Symposium on Generation and Amplification of Asymmetry in Chemical Systems, Jülich, September 24–26, 1973.     

Environmental Change, Injustice and Sustainability

This paper argues that a combination of increasing inequality, hypocrisy, population growth and adverse global environmental change imperils our civilisation. Selected examples of existing inequality and the immoral treatment of human beings are provided from countries of the Asia Pacific. There is also limited discussion of the global eco-social crisis, stressing the links between environmental scarcity and the human responses of resentment, conflict, terrorism and ill-governance. The essay contends that just as the lives of unborn humans similar to us are of interest and value to bio-ethicists, so too should be the lives and descendants of people who are unlike us, even if such people are perceived to be substantially different to ourselves in terms of status, culture and spending power. It is argued that it is in the interests of ourselves, society, and global civilisation that the lives of such people are considered and where possible improved in order to foster the “sustainability transition” needed to secure our collective future. The essay concludes with a discussion of an important element for securing our future: the development and implementation of alternative economic systems which will provide more accurate indicators of global progress.     

Actual numbers and effects of recreational disturbance on the distribution and behaviour of Greylag Geese (Anser Anser) in the Neusiedler See – Seewinkel National Park Area

The Neusiedler See – Seewinkel National Park area is confronted with a remarkable increase in tourism and recreational activities during the last years. The “Koppel” area, situated on the eastern shore of the lake, is one of the most important breeding sites for Greylag Geese. Behaviour and distribution of the geese on the breeding site as well as touristic activities on the adjacent road leading along the Koppel were examined to investigate relations and interactions between the Greylag Goose population and tourism. Taking into account the excellent weather and breeding conditions in the year 2000 the results of the survey indicate a stable or even rising Greylag population, increasing numbers of visitors and high disturbance frequencies in the vicinity of the study area. The number of disturbances on the adjacent road seems to affect the suitability of the site in general, leading to a specific temporal and spatial distribution of the birds, whereas different disturbance qualities result in changes of the birds behaviour.     

Electron microscopy holdings of the Protein Data Bank: the impact of the resolution revolution,new validation tools,and implications for the future

As a discipline, structural biology has been transformed by the three-dimensional electron microscopy (3DEM) “Resolution Revolution” made possible by convergence of robust cryo-preservation of vitrified biological materials, sample handling systems, and measurement stages operating a liquid nitrogen temperature, improvements in electron optics that preserve phase information at the atomic level, direct electron detectors (DEDs), high-speed computing with graphics processing units, and rapid advances in data acquisition and processing software. 3DEM structure information (atomic coordinates and related metadata) are archived in the open-access Protein Data Bank (PDB), which currently holds more than 11,000 3DEM structures of proteins and nucleic acids, and their complexes with one another and small-molecule ligands (~ 6% of the archive). Underlying experimental data (3DEM density maps and related metadata) are stored in the Electron Microscopy Data Bank (EMDB), which currently holds more than 21,000 3DEM density maps. After describing the history of the PDB and the Worldwide Protein Data Bank (wwPDB) partnership, which jointly manages both the PDB and EMDB archives, this review examines the origins of the resolution revolution and analyzes its impact on structural biology viewed through the lens of PDB holdings. Six areas of focus exemplifying the impact of 3DEM across the biosciences are discussed in detail (icosahedral viruses, ribosomes, integral membrane proteins, SARS-CoV-2 spike proteins, cryogenic electron tomography, and integrative structure determination combining 3DEM with complementary biophysical measurement techniques), followed by a review of 3DEM structure validation by the wwPDB that underscores the importance of community engagement.