Density dependence and population dynamics of black rhinos (Diceros bicornis michaeli) in Kenya’s rhino sanctuaries

Density‐dependent feedback mechanisms provide insights into the population dynamics and interactions of large herbivores with their ecosystem. Sex ratio also has particularly important implications for growth rates of many large mammal populations through its influence on reproductive potential. Therefore, the interrelationships between density‐dependent factors, comprising density, sex ratio and underlying growth rates (r) were examined for the Eastern black rhino (Diceros bicornis michaeli) living in three rhino sanctuaries in Kenya using four population models. The exponential and logistic models gave similar results and the former were accepted because they better portrayed the actual situation on the ground. Sex ratios in all sanctuary populations were positively correlated with r but interpreted with realization of other factors also affecting r. We caution that the results of population models should be interpreted alongside ground‐truthed observations. We recommend that future translocation strategies should take into account sex and age structures of the donor population, while future studies of density dependence should take into account both biotic and abiotic factors.     

Synthesis of coumarin-polyamine-based molecular probe for the detection of hydroxyl radicals generated by gamma radiation

To develop a molecular probe for detection of hydroxyl radicals in the vicinity of DNA, the coumarin-polyamine complexes, N(1),N(12)-bis[2-oxo-2H-chromene-3-carbonyl]-1,12-diamine-4,9-diazadodecane (5) and tris[2-(2-oxo-2H-chromene-3-carboxamido)ethyl]amine (7), and their hydroxylated derivatives, N(1),N(12)-bis[7-hydroxy-2-oxo-2H-chromene-3-carbonyl]-1,12-diamine-4,9-diazadodecane (6) and tris[2-(7-hydroxy-2-oxo-2H-chromene-3-carboxamido)ethyl]amine (8), have been synthesized. Using computer-generated molecular modeling, the derivatives have been docked onto DNA dodecamer d(CGCGAATTCGCG)(2), the ligand-DNA complexes have been minimized, and the free binding energies (DeltaG(binding)) and inhibition constants (K(i)) have been calculated. Compound 7 is not water-soluble at the concentrations required for the project. When aqueous solutions of 5 are irradiated with gamma rays, the relationship between induced fluorescence and dose is linear in the range of 0 to 10 Gy. The fluorescence emission spectrum of irradiated 5 is similar to that of its dihydroxy derivative 6, indicating conversion of 5 to 6, and induction of fluorescence records formation of hydroxyl radicals in aqueous solution. The dicoumarin-polyamine 5, a novel compound for the detection of hydroxyl radicals close to DNA, is a sensitive and quantitative probe with potential for applications in biological systems.     

Erythrocyte surface sialic acid levels of clinically healthy mongrel and exotic (alsatian and terrier) breeds of dogs

The erythrocyte surface sialic acid concentration of clinically healthy mongrel and exotic (Alsatian i.e. German shepherd and Terrier) breeds of dogs was analyzed in order to determine their role in the genetic resistance of these breeds of dogs to diseases that cause anaemia. The mean erythrocyte surface sialic acid (ESA) concentration was 57.08 ± 1.67, 34.50 ± 2.30 and 20.20 ± 3.54 mg/dl for Mongrel, Alsatian (German shepherd) and Terrier breeds of dogs, respectively, on acid hydrolysis. The mean values of ESA obtained following enzymic hydrolysis of haemoglobin-free erythrocyte membranes using Clostridium chauvoei (Jakari strain) sialidase were 49.08 ± 0.41, 30.97 ± 1.82 and 18.64 ± 0.75 mg/dl for Mongrel, Alsatian (German shepherd) and Terrier dogs respectively. When Trypanosoma vivax sialidase was used the ESA values obtained were 50.81 ± 0.37, 41.70 ±  0.94 and 19.65 + 0.65 mg/dl for Mongrel, Alsatian (German shepherd) and Terrier breeds of dogs respectively. This represents a statistically significant difference (P < 0.001) between the mean ESA concentration of all the breeds of dogs investigated in this study. The higher mean ESA concentration in Mongrel dogs, compared to the exotic breeds may be responsible for their resistance to disease conditions, whose aetiologic agents produce neuraminidase and also cause anaemia.     

Exocyclic amino groups of flanking guanines govern sequence-dependent adduct conformations and local structural distortions for minor groove-aligned benzo[a]pyrenyl-guanine lesions in a GG mutation hotspot context

The environmental carcinogen benzo[a]pyrene (BP) is metabolized to reactive diol epoxides that bind to cellular DNA by predominantly forming N²-guanine adducts (G*). Mutation hotspots for these adducts are frequently found in 5′-···GG··· dinucleotide sequences, but their origins are poorly understood. Here we used high resolution NMR and molecular dynamics simulations to investigate differences in G* adduct conformations in 5′-···CG*GC··· and 5′-···CGG*C··· sequence contexts in otherwise identical 12-mer duplexes. The BP rings are positioned 5′ along the modified strand in the minor groove in both cases. However, subtle orientational differences cause strong distinctions in structural distortions of the DNA duplexes, because the exocyclic amino groups of flanking guanines on both strands compete for space with the BP rings in the minor groove, acting as guideposts for placement of the BP. In the 5′-···CGG*C··· case, the 5′-flanking G · C base pair is severely untwisted, concomitant with a bend deduced from electrophoretic mobility. In the 5′-···CG*GC··· context, there is no untwisting, but there is significant destabilization of the 5′-flanking Watson–Crick base pair. The minor groove width opens near the lesion in both cases, but more for 5′-···CGG*C···. Differential sequence-dependent removal rates of this lesion result and may contribute to the mutation hotspot phenomenon.     

Organization of the aerotaxis receptor aer in the membrane of Escherichia coli

The Aer receptor guides Escherichia coli to specific oxygen and energy-generating niches. The input sensor in Aer is a flavin adenine dinucleotide-binding PAS domain, which is separated from a HAMP/signaling output domain by two membrane-spanning segments that flank a short (four-amino-acid) periplasmic loop. In this study, we determined the overall membrane organization of Aer by introducing combinations of residues that allowed us to differentiate intradimeric collisions from interdimeric collisions. Collisions between proximal residues in the membrane anchor were exclusively intra- or interdimeric but, with one exception, not both. Cross-linking profiles were consistent, with a rigid rather than flexible periplasmic loop and a tilted TM2 helix that crossed TM2' at residue V197C, near the center of the lipid bilayer. The periplasmic loop formed a stable neighborhood that (i) included a maximum of three Aer dimers, (ii) did not swap neighbors over time, and (iii) appeared to be constrained by interactions in the cytosolic signaling domain.     

Small conformationally restricted piperidine N-arylsulfonamides as orally active gamma-secretase inhibitors

The design and development of a new class of small 2,6-disubstituted piperidine N-arylsulfonamide gamma-secretase inhibitors is reported. Lowering molecular weight including the use of conformational constraint led to compounds with less CYP 3A4 liability compared to early leads. Compounds active orally in lowering Abeta levels in Tg CRND8 mice were identified as potential treatments for Alzheimer's disease.     

Smear cytology in the intra-operative assessment of periodontoid pseudotumour of the craniocervical junction

OBJECTIVE: Periodontoid pseudotumours are lesions of presumed degenerative aetiology which typically occur in elderly patients with cervical myelopathy. The clinical and radiological differential diagnosis includes neoplastic and inflammatory lesions, and the exclusion of such lesions may be of value in the intra-operative management of the patient. This audit aimed to examine the value of intra-operative smear cytology in the management of this condition. METHODS: The intra-operative smear cytological features of four cases of periodontoid pseudotumour were reviewed. RESULTS: In each case the intra-operative cytological interpretation was in keeping with a non-neoplastic and non-inflammatory process. CONCLUSION: These results suggest that intra-operative smear cytology can provide information on the value in the intra-operative management of patients with this lesion.