Synthesis and biological characterisation of ester and amide derivatives of fusidic acid as antiplasmodial agents

A series of novel fusidic acid (FA) derivatives was synthesized by replacing the carboxylic acid group with various ester and amide groups and evaluated in vitro for their antiplasmodial activity against the chloroquine-sensitive NF54 and multidrug-resistant K1 strains of the malarial parasite Plasmodium falciparum. Most of these derivatives showed a 4–49 and 5–17-fold increase in activity against NF54 and KI strains, respectively, as compared to FA and had a good selectivity index. These derivatives are stable over the incubation period and do not appear to be prodrugs of fusidic acid.     

The effect of growth factors on anoxic chemostat cultures of two Saccharomyces cerevisiae strains

In anoxic chemostat cultures of Saccharomyces cerevisiae ATCC 4126 and CBS 8066 grown in a medium containing yeast extract, a sharp increase in the steady-state residual glucose concentration occurred at relatively low dilution rates, contrary to the expected Monod kinetics. However, supplementation with vitamins and amino acids facilitated efficient glucose uptake. This enhanced requirement for growth factors under anoxic conditions and at high growth rates could explain the exceptionally high apparent k _s values for S. cerevisiae reported in the literature.     

A high-density consensus map of barley to compare the distribution of QTLs for partial resistance to Puccinia hordei and of defence gene homologues

A consensus map of barley was constructed based on three reference doubled haploid (DH) populations and three recombinant inbred line (RIL) populations. Several sets of microsatellites were used as bridge markers in the integration of those populations previously genotyped with RFLP or with AFLP markers. Another set of 61 genic microsatellites was mapped for the first time using a newly developed fluorescent labelling strategy, referred to as A/T labelling. The final map contains 3,258 markers spanning 1,081 centiMorgans (cM) with an average distance between two adjacent loci of 0.33 cM. This is the highest density of markers reported for a barley genetic map to date. The consensus map was divided into 210 BINs of about 5 cM each in which were placed 19 quantitative trait loci (QTL) contributing to the partial resistance to barley leaf rust (Puccinia hordei Otth) in five of the integrated populations. Each parental barley combination segregated for different sets of QTLs, with only few QTLs shared by any pair of cultivars. Defence gene homologues (DGH) were identified by tBlastx homology to known genes involved in the defence of plants against microbial pathogens. Sixty-three DGHs were located into the 210 BINs in order to identify candidate genes responsible for the QTL effects. Eight BINs were co-occupied by a QTL and DGH(s). The positional candidates identified are receptor-like kinase, WIR1 homologues and several defence response genes like peroxidases, superoxide dismutase and thaumatin. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Mechanical stresses in carotid plaques using MRI-based fluid-structure interaction models

Risk assessment in patients with carotid atherosclerosis relies on the degree of luminal stenosis. Incorporating morphological information on plaque composition obtained noninvasively through the use of magnetic resonance imaging (MRI) could include other variables besides the degree of stenosis into carotid plaque risk assessment. Knowledge of the morphologic composition of the plaque allows determination of mechanic stresses exerted on the protective fibrous cap, which may be of importance in the assessment of plaque vulnerability. Based on image processing of transverse MRI scans, longitudinal 2D fluid-structure interaction (FSI) simulations of carotid atherosclerotic plaques were performed facilitating in-vivo estimation of longitudinal internal fibrous cap stresses. The FSI simulation combined finite element analysis (FEA) with computational fluid dynamics (CFD) simulations of blood-flow variables. Preliminary results from two symptomatic patients revealed longitudinal stress levels (max. 254.1 and 143.2 kPa) approaching established criteria for plaque rupture at known predilection sites of plaque rupture. Determination of longitudinal fibrous cap stresses may prove useful in assessing plaque vulnerability and improve risk stratification in patients with carotid atherosclerosis.     

The value of lipid composition in the taxonomy of the Schizosaccharomycetales

In this study, the lipid fractions i.e. neutral (NL), phospho-(PL) and glycolipids (GL) with associated fatty acids (FAs) of 54 strains, representing the Schizosaccharomycetales, were analyzed during stationary growth phase and compared. Trace amounts of linoleic acid (18:2) were present in most of the strains representing Schizosaccharomyces. An increased percentage 18:2 was observed in the PL fraction when compared to the NL fraction. This is possibly related to membranes requiring polyunsaturated FAs for fluidity. On the basis of the percentage oleic acid (18:1) and 18:2 FAs in the different lipid fractions, the Schizosaccharomycetales can clearly be divided into two groups i.e. Group 1 (represented by the genus Hasegawaea) comprising strains producing relatively large amounts of 18:2 and relatively low amounts of 18:1 when compared to Group 2 (represented by the genus Schizosaccharomyces comprising Schizosaccharomyces octosporus and Schizosaccharomyces pombe). These results are in accordance with 18S and 26S rRNA base sequence analyses and emphasize the difference between the genera Hasegawaea and Schizosaccharomyces. Utilizing gas chromatography-mass spectrometry analyses, it was found that these strains were all capable of producing gamma-linolenic acid. This further emphasizes the uniqueness of this order in the Dikaryomycota.     

Respiratory energy requirements and rate of protein turnover in vivo determined by the use of an inhibitor of protein synthesis and a probe to assess its effect

Protein turnover is generally regarded as a major maintenance process, but experimental evidence to support this contention is scarce. Here we quantify the component of dark respiration rate associated with overall protein turnover of tissues in vivo. The effect of an inhibitor of cytosolic protein synthesis (cycloheximide, CHM) on dark respiration was tested on a cell suspension from potato ( Solanum tuberosum L.) and quantified on leaf discs of expanding and full-grown primary leaves of bean ( Phaseolus vulgaris L.). The in vivo effect of CHM on protein biosynthesis was assessed by monitoring the inhibition of the induction of the ethylene-forming enzyme (EFE) activity. The present method yields the energy costs of turnover of the total pool of proteins irrespective of their individual turnover rates. Average turnover rates were derived from the respiratory costs and the specific costs for turnover.
Inhibition of respiration by CHM was readily detectable in growing-cell suspensions and discs of expanding leaves, The derived respiratory costs of protein turnover in expanding leaves were maximally 17–37% of total respiration. Turnover costs in full-grown primary leaves of bean amounted to 17–21% of total dark respiration. The maximum degradation constants (i.e. K_d-values) derived for growing and full-grown leaves were up to 2.42 × 10⁻⁶ and 1.12 × l0⁻⁶ s⁻¹, respectively.     

Molecular phylogeny of the critically endangered Hunter's antelope (Beatragus hunteri Sclater 1889)

The phylogenetic relationships of Hunter's antelope or hirola Beatragus hunteri (Artiodactyla: Alcelaphini), one of the most seriously threatened antelopes in Africa, have been the subject of controversial discussion. A total of 801 base pairs of the mitochondrial cytochrome b gene were determined from five alcelaphine species and from two nonalcelaphine bovids. Phylogenetic analysis using parsimony, maximum likelihood, and distance methods identified a single best-supported hypothesis of evolutionary relationships within the Alcelaphini: (i) monophyly of the tribe, (ii) most basal position of the blue wildebeest, (iii) sister-grouping of the Lichtenstein's and Coke's hartebeests, (iv) phylogenetic distinctiveness of the hirola from the topi and the hartebeests. We deduce that the alcelaphine cytochrome b sequences began to diverge from a common mitochondrial ancestor about 5.5 million years ago. In addition, we provide molecular evidence that the impala Aepyceros melampus is not closely related to Alcelaphini.     

Diet of Mackinder's eagle owl Bubo capensis mackinderi in the alpine zone of Mount Kenya

The diet of Bubo capensis mackinderi Sharpe in the alpine zone of Mt. Kenya was studied by analysing pellets collected from nesting and roosting sites in four different valleys. Overall, mammals comprised 97.4% of prey individuals and 98.9% of the ingested biomass. Rodents, mainly groove‐toothed rats, were the owl's staple food in all four valleys, but rock hyrax, insectivores and birds were also consumed. Proportions of rock hyrax, rodents and insectivores did not differ between the valleys. Total dietary composition in the different valleys showed a high degree of overlap in proportions of main prey types averaging 93.2% in percentage of occurrence and 85.0% in percentage of biomass.     

Versuche zur Protoplastenregeneration dikotyler Pflanzen unterschiedlicher systematischer Zugehörigkeit

Die beschriebenen Experimente, die bisher mit 63 Pflanzenarten durchgeführt wurden, erbrachten Protoplastenteilungen bei 42 Arten, Bildung von wüchsigem Kallus bei 22 Arten, von Wurzeln als einzigen Organen bei vier Arten und von Sprossen bei zwölf weiteren Arten. Bei acht dieser Arten gelang bereits die Aufzucht von Pflanzen. Mit den gesammelten Informationen scheinen erste Fortschritte auf dem Weg zur Standardisierung der Protoplastenregeneration dikotyler Pflanzen möglich zu sein. So erwiesen sich Sproßspitzen als leicht verfügbares Material, aus dem Protoplasten geeigneter Differenzierung gewonnen werden konnten. Unter Gewebekulturbedingungen herangezogene Sprosse waren, vor allem auf Grund des Fehlens von Kontaminationen, Pflanzen von Erdkulturen vorzuziehen. Protoplastenteilungen der diversen Taxa angehörenden Pflanzen wurden durch das Kulturmedium V-KM ermöglicht, insbesondere bei Verwendung von Sproßspitzen als Ausgangsmaterial. Anfänglich hohe Zelldichten, schrittweise Verdünnung der Suspensionen und Übertragung auf V-KM-Bodenagar einige Tage vor der Erhöhung der Turgeszenz erwiesen sich in der Regel als vorteilhaft. Wir danken Frau J. Finger und Fräulein G. Mordhorst für ihre technische Mitarbeit. Die Experimente wurden durch eine Beihilfe der Deutschen Forschungsgemeinschaft gefördert.