Interaction between beta-cyclodextrin and 1,10-phenanthroline: uncommon 2:3 inclusion complex in the solid state

The crystallographic structure of the complex formed by beta-cyclodextrin with 1,10-phenanthroline has been studied by X-ray diffraction. The result shows that the complex adopts an uncommon 2:3 stoichiometry in solid state, that is, every complex unit contains three 1,10-phenanthroline molecules and two beta-cyclodextrin molecules, where two 1,10-phenanthroline molecules individually occupy two cyclodextrin cavities, and the third guest molecule is located in the interstitial space between two head-to-head cyclodextrin molecules. The intermolecular hydrogen bonds between the adjacent complex units further link these individual monomers to a channel-type assembly. Furthermore, 1H and 2D NMR spectroscopy has been employed to investigate the inclusion behavior between the host beta-cyclodextrin and guest 1,10-phenanthroline in aqueous solution.     

Inclusion complexes of V-amylose with undecanoic acid and dodecanol at atomic resolution: X-ray structures with cycloamylose containing 26 D-glucoses (cyclohexaicosaose) as host

Crystal structures are reported of cycloamylose containing 26 D-glucose residues (CA26, cyclohexaicosaose, C156H260O130) in complexes with undecanoic acid (CA26 x 2C10H21COOH x 34.95 H2O, orthorhombic P2(1)2(1)2(1), one CA26 and two bound undecanoic acids F1 and F2 in the asymmetric unit, resolution 0.95 angstroms) and with dodecanol ((CA26)(0.5) x C12H25OH x 32.0H2O, monoclinic C2, half a CA26 binding one dodecanol, A, in the asymmetric unit, resolution 1.0 angstroms). The macrocycle of CA26 is folded like the figure '8' into two 10 D-glucoses long left-handed V-amylose helices forming approximately 5A wide V-channels that are occupied by undecanoic acid (F1, F2) or dodecanol (A) as guest molecules. The functional head groups of the guests near the O(6) ends of the V-channels are hydrogen bonded with d-glucose O(6)n-H; the aliphatic termini beyond C(9) protrude from the O(2), O(3) ends. Parts of the aliphatic chains enclosed in the V-channels are all-trans except for one torsion angle each (approximately 130 degrees ) in undecanoic acid molecules F1 and F2. There are several (guest)C-H...O hydrogen bonds to O(4) and O(6) of CA26 in both complexes, and H...H van der Waals interactions with d-glucose C(3)-H and C(5)-H dominate. C(5)-H determine the position of the aliphatic chains of undecanoic acid F1 and of dodecanol A in contrast to F2 where both C(3)-H and C(5)-H contribute equally, probably because the V-channel is narrower than in F1 and in dodecanol. Complexes of polymeric V-amylose with fatty acids and alcohols studied by X-ray fiber diffraction could not provide the here described high resolution.     

Animal models of idiosyncratic drug reactions

Idiosyncratic drug reactions represent a major problem. In most cases the mechanisms of these reactions are unknown, but circumstantial evidence points to the involvement of reactive metabolites and the characteristics of the reactions suggest involvement of the immune system. If progress is to be made in dealing with these adverse reactions it is essential that we have a better understanding of their mechanisms, and it is hard to imagine testing mechanistic hypotheses without good animal models. Unfortunately, idiosyncratic reactions are also idiosyncratic in animals so few good models exist. The best models, in which a rodent develops a clinical syndrome similar to that which occurs in humans, appear to be penicillamine-induced autoimmunity in Brown Norway rats and nevirapine-induced skin rash in rats. Sulfamethoxazole-induced hypersensitivity in dogs and propylthiouracil-induced autoimmunity in cats are also similar to adverse reactions that occur in people, but they have practical limitations. Halothane-induced liver toxicity in guinea pigs and amodiaquine-induced bone marrow and liver toxicity in rats represent models in which there is an immune response and mild, reversible toxicity. It is possible that the development of immune tolerance is what limits the toxicity in these models, and if this is true, interventions that prevent tolerance might lead to good models. Although the history of developing animal models of idiosyncratic drug reactions is mostly one of failure, such models are essential. A better understanding of immune tolerance may greatly facilitate the development of better models; transgenic technology may also provide an important tool.     

Multiple Cos2/Ci interactions regulate Ci subcellular localization through microtubule dependent and independent mechanisms

The Hedgehog (Hh) family of secreted proteins governs many developmental processes in both vertebrates and invertebrates. In Drosophila, Hh acts by blocking the formation of a truncated repressor form of Cubitus interruptus (Ci) and by stimulating the nuclear translocation and activity of full-length Ci (Ci155). In the absence of Hh, Ci155 is sequestered in the cytoplasm by forming protein complexes with Costal2 (Cos2), Fused (Fu) and Suppressor of Fused [Su(fu)]. How complex formation regulates Ci155 subcellular localization is not clear. We find that Cos2 interacts with two distinct domains of Ci155, an amino (N)-terminal domain (CDN) and a carboxyl (C)-terminal domain (CORD), and Cos2 competes with Su(fu) for binding to the N-terminal region of Ci155. We provide evidence that both N- and C-terminal Cos2 binding domains are involved in the cytoplasmic retention of Ci155 in imaginal discs. Treating imaginal discs with microtubule-destabilizing reagent nocodazole promotes nuclear translocation of Ci155, suggesting that the microtubule network plays an important role in the cytoplasmic retention of Ci155. In addition, we find that adding a nuclear localization signal (NLS) to exposed regions of Ci155 greatly facilitates its nuclear translocation, suggesting that the cytoplasmic retention of Ci155 may also depend on NLS masking.     

DOES LINKAGE DISEQUILIBRIUM GENERATE HETEROZYGOSITY‐FITNESS CORRELATIONS IN GREAT REED WARBLERS?

Heterozygosity-fitness correlations (HFCs) at noncoding genetic markers are commonly assumed to reflect fitness effects of heterozygosity at genomewide distributed genes in partially inbred populations. However, in populations with much linkage disequilibrium (LD), HFCs may arise also as a consequence of selection on fitness loci in the local chromosomal vicinity of the markers. Recent data suggest that relatively high levels of LD may prevail in many ecological situations. Consequently, LD may be an important factor, together with partial inbreeding, in causing HFCs in natural populations. In the present study, we evaluate whether LD can generate HFCs in a small and newly founded population of great reed warblers (Acrocephalus arundinaceus). For this purpose dyads of full siblings of which only one individual survived to adult age (i.e., returned to breed at the study area) were scored at 19 microsatellite loci, and at a gene region of hypothesized importance for survival, the major histocompatibility complex (MHC). By examining siblings, we controlled for variation in the inbreeding coefficient and thus excluded genome-wide fitness effects in our analyses. We found that recruited individuals had significantly higher multilocus heterozygosity (MLH), and mean d2 (a microsatellite-specific variable), than their nonrecruited siblings. There was a tendency for the survivors to have a more diverse MHC than the nonsurvivors. Single-locus analyses showed that the strength of the genotype-survival association was especially pronounced at four microsatellite loci. By using genotype data from the entire breeding population, we detected significant LD between five of 162 pairs of microsatellite loci after accounting for multiple tests. Our present finding of a significant within-family multilocus heterozygosity-survival association in a nonequilibrium population supports the view that LD generates HFCs in natural populations.     

Fecundity and MHC affects ejaculation tactics and paternity bias in sand lizards

We demonstrate that extending copulation enhances probability of paternity in sand lizards and that determinants of copulation duration depend on a males' mating order (first or second). First males, with no information on presence of rivals, extend copulation when mating with a more fecund female. Second males, however, adjust copula duration in relation to a first male's relatedness with his female, which there is reason to believe can be deduced from the MHC-related odor of the copulatory plug. Male-female relatedness negatively influences a male's probability of paternity, and when second males are in a favored role (i.e., the first male is the one more closely related to the female), second males transfer larger ejaculates, resulting in higher probability of paternity. This result corroborates predictions from recent theoretical models on sperm expenditure theory incorporating cryptic female choice and sexual conflict. More specifically, the results conform to a "random roles" model, which depicts males as being favored by some females and disfavored by others, but not to a "constant-type" model, in which a male is either favored or disfavored uniformly by all females in a population.     

Mismatch repair proteins, meiosis, and mice: understanding the complexities of mammalian meiosis

Mammalian meiosis differs from that seen in lower eukaryotes in several respects, not least of which is the added complexity of dealing with chromosomal interactions across a much larger genome (12 MB over 16 chromosome pairs in Saccharomyces cerevisiae compared to 2500 MB over 19 autosome pairs in Mus musculus). Thus, the recombination machinery, while being highly conserved through eukaryotes, has evolved to accommodate such issues to preserve genome integrity and to ensure propagation of the species. One group of highly conserved meiotic regulators is the DNA mismatch repair protein family that, as their name implies, were first identified as proteins that act to repair DNA mismatches that arise primarily during DNA replication. Their function in ensuring chromosomal integrity has also translated into a critical role for this family in meiotic recombination in most sexually reproducing organisms. In mice, targeted deletion of certain family members results in severe consequences for meiotic progression and infertility. This review will focus on the studies involving these mutant mouse models, with occasional comparison to the function of these proteins in other organisms.     

Discovery of the catalytic function of a putative 2-oxoacid dehydrogenase multienzyme complex in the thermophilic archaeon Thermoplasma acidophilum

Those aerobic archaea whose genomes have been sequenced possess a single 4-gene operon that, by sequence comparisons with Bacteria and Eukarya, appears to encode the three component enzymes of a 2-oxoacid dehydrogenase multienzyme complex. However, no catalytic activity of any such complex has ever been detected in the Archaea. In the current paper, we have cloned and expressed the first two genes of this operon from the thermophilic archaeon, Thermoplasma acidophilum. We demonstrate that the protein products form an alpha2beta2 hetero-tetramer possessing the decarboxylase catalytic activity characteristic of the first component enzyme of a branched-chain 2-oxoacid dehydrogenase multienzyme complex. This represents the first report of the catalytic function of these putative archaeal multienzyme complexes.     

Female-induced sexual arousal in male mice and rats: behavioral and testosterone response

Exposure of a male mouse to a female mouse separated from it by a holed partition induced specific behavior and an increase in blood testosterone in the male. The male made more approaches to the partition and spent more time at it. The time spent by the male mouse over the first 10 min at the partition, behind which an estrus female was placed, was increased sixfold compared to the time spent by a male mouse exposed to the vacant neighboring compartment; and 1.5-fold compared to that spent by a male mouse exposed to a nonreceptive female or a male. Increased blood testosterone level was detected at 20 min of exposure to a receptive female in winter and at 40 min in summer. No variation in blood testosterone levels in the male mouse exposed to a nonreceptive female or a male was observed. Similar response to a receptive female placed in the neighboring compartment was shown in a male rat. The time spent by the male rat at the partition was 12 times higher when there was an estrus female behind it than in control. Blood testosterone in the male rat increased in response to a female rat and did not change in response to a male rat indicating female-induced motivation. It was concluded that the partition time might serve as a quantitative measure of sexual motivation in the males and that the model of female-induced sexual arousal used was suitable for studying both motivational and hormonal components of sexual arousal in male mice and rats.