Vegetation types and patterns in Senegal based on multivariate analysis of field and NOAA-AVHRR satellite data

Abstract. Woody vegetation was studied in 44 sites in Senegal. Species composition and density were analysed with TWINSPAN and Canonical Correspondence Analysis; 16 vegetation types were defined. A supervised, multispectral and multitemporal classification of day and night, dry season NOAA-AVHRR imagery was used to identify their distribution with a classification accuracy ranging from 60–100%.     

Evolution of 1, 3, 5-trisubstituted bipyrazole scaffold based platinum(II) complexes as a biological active agent

Abstract

Square planar mononuclear platinum(II) complexes having general formula [Pt(Lⁿ)Cl₂], (where, Lⁿ?=?L^1–4) were synthesized with neutral bidentate heterocyclic 1,3,5-trisubstituted bipyrazole based ligands. The synthesized compounds were characterized by physicochemical method such as TGA, molar conductance, micro-elemental analysis and magnetic moment, and spectroscopic method such as, FT-IR, UV–vis, ¹H NMR, ¹³C NMR and mass spectrometry. Biological applications of the compounds were carried out using in vitro brine shrimp lethality bioassay, in vitro antimicrobial study against five different pathogens, and cellular level cytotoxicity against Schizosaccharomyces pombe (S. Pombe) cells. Pt(II) complexes were tested for DNA interaction activities using electronic absorption titration, viscosity measurements study, fluorescence quenching technique and molecular docking assay. Binding constants (K_b) of ligands and complexes were observed in the range of 0.23–1.07?×?10⁵?M^?1 and 0.51–3.13?×?10⁵?M^?1, respectively. Pt(II) complexes (I–IV) display an excellent binding tendency to biomolecule (DNA) and possess comparatively high binding constant (K_b) values than the ligands. The DNA binding study indicate partial intercalative mode of binding in complex-DNA. The gel electrophoresis activity was carried out to examine DNA nuclease property of pUC19 plasmid DNA.     

Crystal structure of quinone reductase 2 in complex with cancer prodrug CB1954

CB1954 is a cancer pro-drug that can be activated through reduction by Escherichia coli nitro-reductases and quinone reductases. Human quinone reductase 2 is very efficient in the activation of CB1954, approximately 3000 times more efficient than human QR1 in terms of k(cat)/K(m). We have solved the three-dimensional structure of QR2 in complex with CB1954 to a nominal resolution of 1.5A. The complex structure indicates the essentiality of the two nitro groups: one nitro group forms hydrogen bonds with the side-chain of Asn161 of QR2 to hold the other nitro group in position for the reduction. We further conclude that residue 161, an Asn in QR2 and a His in QR1, is critical in differentiating the substrate specificities of these two enzymes. Mutation of Asn161 to His161 in QR2 resulted in the total loss of the enzymatic activity towards activation of CB1954, whereas the rates of reduction towards menadione are not altered.     

Identification and characterization of the mitochondrial membrane sorting signals in phosphatidylserine decarboxylase 1 from Saccharomyces cerevisiae

Phosphatidylserine decarboxylase 1 (Psd1p) catalyzes the formation of the majority of phosphatidylethanolamine (PE) in the yeast Saccharomyces cerevisiae. Psd1p is localized to mitochondria, anchored to the inner mitochondrial membrane (IMM) through membrane spanning domains and oriented towards the mitochondrial intermembrane space. We found that Psd1p harbors at least two inner membrane-associated domains, which we named IM1 and IM2. IM1 is important for proper orientation of Psd1p within the IMM (Horvath et al., J. Biol. Chem. 287 (2012) 36744–55), whereas it remained unclear whether IM2 is important for membrane-association of Psd1p. To discover the role of IM2 in Psd1p import, processing and assembly into the mitochondria, we constructed Psd1p variants with deletions in IM2. Removal of the complete IM2 led to an altered topology of the protein with the soluble domain exposed to the matrix and to decreased enzyme activity. Psd1p variants lacking portions of the N-terminal moiety of IM2 were inserted into IMM with an altered topology. Psd1p variants with deletions of C-terminal portions of IM2 accumulated at the outer mitochondrial membrane and lost their enzyme activity. In conclusion we showed that IM2 is essential for full enzymatic activity, maturation and correct integration of yeast Psd1p into the inner mitochondrial membrane.     

Litter fall and nutrient dynamics in a Nigerian rain forest seven years after a ground fire

Abstract. Seasonal litter fall and mineral element content (N, P, Ca, Mg, K) of regrowth forest communities at the base and on the slope of an inselberg in Ile-Ife, Nigeria, were studied 7 yr after a ground fire ravaged the forest. Litter fall (tha^?1 yr^?1) was 4.6 (total), 4.2 (leaf), 0.3 (small wood < 2.5 cm diameter) and 0.1 (reproductive parts: fruits and flowers) in the base community and 6.4 (total), 5.4 (leaf), 0.9 (small wood) and 0.1 (reproductive parts) in the slope community. There was significant monthly variation in litter fall in the two communities with lowest amount of litter recorded during the wettest months of the year (May - August) and the highest amount during the dry season. Significant monthly variation (P<0.05) in Ca, Mg and K concentration in leaf litter and for Mg (P < 0.01) in fruit litter occurred, with the lowest concentration recorded during the wettest months (May-August). In leaf and wood litter the order of mineral element concentration was Ca>N>K> Mg > P while in fruit litter it was N > K > Ca > Mg > P. Quantities of mineral element (kg ha^-1 yr¹) returned to the soil via litterfall were N: 66; P: 4; Ca: 97; Mg: 15; K: 45 in base forest, and N: 112; P: 5; Ca: 142; Mg: 20; K: 66 in slope forest. Through leaf litter >88.5% of these elements was returned into the two communities, through wood > 4.0% and through reproductive organs > 0.3%. The order of quantities of these elements returned in leaf and wood litter was Ca > N > K > Mg > P, in fruit litter N ～ K > Ca > Mg > P. Significant monthly variation in the amounts of the various elements returned were recorded in leaf litter, but not in wood and fruit litter. The lowest amount of various elements was returned during the wettest months (May-August) which coincided with the period of the lowest element concentration and litter fall.     

A test for spatial relationships between neighbouring plants in plots of heterogeneous plant density

Abstract. Maps of plant individuals in (x, y) coordinates (i.e. point patterns) are currently analysed through statistical methods assuming a homogeneous distribution of points, and thus a constant density within the study area. Such an assumption is seldom met at the scale of a field plot whilst delineating less heterogeneous subplots is not always easy or pertinent. In this paper we advocate local tests carried out in quadrats partitioning the plot and having a size objectively determined via a trade‐off between squared bias and variance. In each quadrat, the observed pattern of points is tested against complete spatial randomness (CSR) through a classical Monte‐Carlo approach and one of the usual statistics. Local tests yield maps of p‐values that are amenable to diversified subsequent analyses, such as computation of a variogram or comparison with co‐variates. Another possibility uses the frequency distribution of p‐values to test the whole point pattern against the null hypothesis of an inhomogeneous Poisson process. The method was demonstrated by considering computer‐generated inhomoge‐neous point patterns as well as maps of woody individuals in banded vegetation (tiger bush) in semi‐arid West Africa. Local tests proved able to properly depict spatial relationships between neighbours in spite of heterogeneity/clustering at larger scales. The method is also relevant to investigate interaction between density and spatial pattern in the presence of resource gradients.     

Kinetic and structural characterisation of Escherichia coli nitroreductase mutants showing improved efficacy for the prodrug substrate CB1954

Escherichia coli nitroreductase (NTR) is a flavoprotein that reduces a variety of quinone and nitroaromatic substrates. Among these substrates is the prodrug 5-[aziridin-1-yl]-2,4-dinitrobenzamide (CB1954) that is activated by NTR to form two products, one of which is highly cytotoxic. NTR in combination with CB1954 has entered clinical trials for virus-directed enzyme-prodrug therapy of cancer. Enhancing the catalytic efficiency of NTR for CB1954 is likely to improve the therapeutic potential of this system. We previously identified a number of mutants at six positions around the active site of NTR that showed enhanced sensitisation to CB1954 in an E. coli cell-killing assay. In this study we have purified improved mutants at each of these positions and determined their steady-state kinetic parameters for CB1954 and for the antibiotic nitrofurazone. We have also made a double mutant, combining two of the most beneficial single mutations. All the mutants show enhanced specificity constants for CB1954, and, apart from N71S, the enhancement is selective for CB1954 over nitrofurazone. One mutant, T41L, also shows an increase in selectivity for reducing the 4-nitro group of CB1954 rather than the 2-nitro group. We have determined the three-dimensional structures of selected mutants bound to the substrate analogue nicotinic acid, using X-ray crystallography. The N71S mutation affects interactions of the FMN cofactor, while mutations at T41 and F124 affect the interactions with nicotinic acid. The structure of double mutant N71S/F124K combines the effects of the two individual single mutations, but it gives a greater selective enhancement of activity with CB1954 over nitrofurazone than either of these, and the highest specificity constant for CB1954 of all the mutations studied.     

High-performance liquid chromatographic method for sensitive determination of the alkylating agent CB1954 in human plasma

A high-performance liquid chromatography (HPLC) method is described for the measurement of the weak alkylating agent CB1954 in human plasma. CB1954 can be used as an innocuous prodrug designed for activation by bacterial nitroreductases in strategies of gene-directed enzyme–prodrug therapy, and becomes activated to a potent bifunctional alkylating agent. The HPLC method involves precipitation and solvent extraction and uses Mitomycin C (MMC) as an internal standard, with a retention time for MMC of 5.85±0.015 min, and for CB1954 of 10.72±0.063 min. The limit of detection for CB1954 is 2.9 ng/ml, and this compares favourably with systems involving direct analysis of plasma (limit of detection 600 ng/ml, approximately). The method is now being used for pharmacokinetic measurements in plasma samples from cancer patients entering phase I clinical trials of CB1954. Results using serial plasma samples from one patient are presented. The patient was treated intravenously with CB1954 (6 mg/m²), and plasma clearance of the drug showed biphasic kinetics with α half-life 14.6 min, and β half-life 170.5 min.     

Differences between banded thickets (tiger bush) at two sites in West Africa

Abstract. This paper deals with the influence of edaphic conditions on the spatial structure of banded thickets or tiger bush (brousse tigrée). It is based on two sites in West Africa, with similar climatic conditions but located on contrasting substrates. The spatial structure was described with standardized characteristics including thicket spacing, thicket/inter‐thicket contrast, upslope/downslope asymmetry and species zonation throughout the vegetation band. Recruitment and senescence features of woody stands were emphasized in order to understand current dynamics. Data were collected on transects oriented perpendicular to the contours and so to the thickets as well. A standardized analytical procedure was applied to data from both sites to ensure consistent and thorough delineation of thickets. The overall periodicity of thickets, the woody flora and the dominant species Combretum micranthum were similar at the two sites. However, thicket spacing, thicket/inter‐thicket contrast and upslope/downslope floristic asymmetry of the thickets were higher in the less favourable site. Also seedlings were less abundant, with a greater dependence on pre‐existing thickets. Not all banded vegetation systems show sharp contrasts and are strongly asymmetric, since such characteristics are likely to be reinforced by adverse environmental conditions. As a consequence, current dynamics may be more diverse than expected. Quantified inter‐site comparisons can greatly help to classify African banded vegetation systems and to discuss potential dynamic outcomes.