bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bayesian approach to the assessment of inhibitor risk in studies of factor VIII concentrates
Authors: Lee M. L. , Roth D. A.
Published: January 2005

Summary.  The assessment of inhibitor risk is a crucial component in the clinical development of new and modified factor VIII (FVIII) preparations. There has been a recent discussion about the design of studies and the assessment of inhibitors and inhibitor risk in such studies at a recent FDA‐sponsored FVIII Inhibitor Workshop, and new requirements for the success of these trials have been proposed to evaluate inhibitor data based on the use of an upper 95% confidence bound. We review the consequences of these requirements and demonstrate that for any product to succeed, it must have an extremely low underlying risk of inhibitor development. Furthermore, several existing commercially available FVIII products with an excellent safety record would not necessarily pass these endpoints. As a result, we propose an alternative set of acceptance criteria based on a Bayesian statistical paradigm. This approach is based on the determination of a probability that the product in question actually has an inhibitor risk below some pre‐set limit, a concept that we believe is more intuitive than the traditional confidence interval method. We show that all existing products would pass this approach, but a product (Bisinact) with known inhibitor risk would not.
Rituximab for autoimmune haemophilia: a proposed treatment algorithm
Authors: Aggarwal A. , Grewal R. , Green R. J. , Boggio L. , Green D. , Weksler B. B. , Wiestner A. , Schechter G. P.
Published: January 2005

Summary.  We previously reported durable complete responses following brief courses of rituximab and prednisone with or without cyclophosphamide in four patients with autoimmune haemophilia and inhibitor titres of 5–60 BU. We report here responses to this monoclonal anti‐CD20 antibody in four additional patients, including two patients with inhibitor titres >200 BU. Factor VIII levels became normal 2–35weeks after 4 or 8 weekly doses of rituximab, brief courses of prednisone and in one patient immunoglobulin. Complete responses are ongoing at 10 months in two patients. Two patients relapsed: a patient whose initial inhibitor titre was 525 BU relapsed at 3.5 months and a long‐term prednisone‐dependent patient at 8.5 months. Both responded to second courses of rituximab and prednisone and are in remission. Our experience suggests that rituximab is a safe and effective addition to immunosuppression with prednisone and cyclophosphamide to treat autoimmune haemophilia, and may permit early discontinuation or even avoidance of these potentially toxic agents. High‐titre inhibitor patients, however, may require multiple courses of rituximab or the addition of cyclophosphamide. Pending randomized studies, we propose an algorithm based on our experience and other reports for incorporating rituximab in the treatment of this rare disorder.
Intracranial haemorrhage as initial presentation of severe haemophilia B: case report and review of Mayo Clinic Comprehensive Hemophilia Center experience
Authors: Rodriguez V. , Schmidt K. A. , Slaby J. A. , Pruthi R. K.
Published: January 2005

Summary.  A neonate who had intracranial haemorrhage (ICH) at birth received a diagnosis of severe haemophilia B at 6 months of age. ICH had been the initial presentation of his bleeding disorder. His family history was negative for haemophilia. Review of our institutional experience as well as the literature indicates that intracranial bleeding as the initial presentation of haemophilia is rare.
Identification of new dinucleotide‐repeat polymorphisms in factor VIII gene using fluorescent PCR
Authors: Kim J.‐W. , Park S.‐Y. , Kim Y.‐M. , Kim J.‐M. , Kim D.‐J. , Ryu H.‐M.
Published: January 2005

Summary.  Haemophilia A is an X‐linked inherited bleeding disorder. Linkage diagnosis using polymorphic markers in the factor VIII gene is used to archive the carrier detection and prenatal diagnosis. The objective of this study was to establish the allele frequency and heterozygosity rate (HR) of two new intragenic markers (Intron 1 and 24) and other markers (Intron 13 and 22) using fluorescent PCR. Five hundred unrelated healthy women were screened and haemophilic family was studied for carrier detection and prenatal diagnosis. We observed five different alleles of Intron 1, 10 of Intron 24, nine of Intron 13 and six of Intron 22. The observed HR for Intron 1, 24, 13 and 22 were 34.0, 35.2, 53.0 and 42.6%, while the expected HR were 33.6, 36.3, 50.1 and 44.3%, respectively. Heterozygosity rate with the combined use of all four intragenic markers was 76.6% (383/500). In prenatal diagnosis of a haemophilic family, a pregnant woman was heterozygous with three intragenic (Intron 1, 13 and 22) and one extragenic St14 VNTR (DXS52) markers. She was considered to be a carrier, and she carried a male foetus by AMXY PCR and chromosome analysis of amniocytes. Foetus did not have mutant haplotype as his uncle, suggesting a normal male status. Our study demonstrates the utility of two new intragenic markers in FVIII gene for carrier detection and prenatal diagnosis of haemophilic families.
Gene expression of ecdysteroid‐regulated gene E74 of the honeybee in ovary and brain
Authors: Paul R. K. , Takeuchi H. , Matsuo Y. , Kubo T.
Published: January 2005

To facilitate studies of hormonal control in the honeybee (Apis mellifera L.), a cDNA for a honeybee homologue of the ecdysteroid‐regulated gene E74 (AmE74) was isolated and its expression was analysed. Northern blot analysis indicated strong expression in the adult queen abdomen, and no significant expression in the adult drone and worker abdomens. In situ hybridization demonstrated that this gene was expressed selectively in the ovary and gut in the queen abdomen. Furthermore, this gene was also expressed selectively in subsets of mushroom body interneurones in the brain of the adult worker bees. These findings suggest that AmE74 is involved in neural function as well as in reproduction in adult honeybees.
Gene expression profiles among immature and adult reproductive castes of the termite Reticulitermes flavipes
Authors: Scharf M. E. , Wu‐Scharf D. , Zhou X. , Pittendrigh B. R. , Bennett G. W.
Published: January 2005

Array‐based genomic studies were conducted with the goal of identifying immature (i.e. nymph) and adult reproductive caste‐biased gene expression in the termite Reticulitermes flavipes. Using cDNA macro‐arrays, we identified thirty‐four nymph‐biased genes falling into eight ontogenic categories. Based on gene expression profiles among diverse castes and developmental stages (determined by quantitative PCR), several important trends emerged. These findings highlight the importance of several developmental and survival‐based factors among immature and adult termite reproductives, including: vitellogenesis, nutrient storage, juvenile hormone sequestration, ribosomal translational and filtering mechanisms, fatty acid biosynthesis, apoptosis inhibition, and both endogenous and symbiont cellulase‐assisted nutrition. These findings are highly significant as they are the first to elucidate the molecular biology underlying termite reproductive caste differentiation and reproductive caste‐specific biology. Other gene expression results are in agreement with previous findings that suggest roles for vitellogenin‐like haemolymph proteins in soldier caste differentiation.
Insect glutathione transferases and insecticide resistance
Authors: Enayati A. A. , Ranson H. , Hemingway J.
Published: January 2005

Glutathione transferases (GSTs) are a diverse family of enzymes found ubiquitously in aerobic organisms. They play a central role in the detoxification of both endogenous and xenobiotic compounds and are also involved in intracellular transport, biosynthesis of hormones and protection against oxidative stress. Interest in insect GSTs has primarily focused on their role in insecticide resistance. GSTs can metabolize insecticides by facilitating their reductive dehydrochlorination or by conjugation reactions with reduced glutathione, to produce water‐soluble metabolites that are more readily excreted. In addition, they contribute to the removal of toxic oxygen free radical species produced through the action of pesticides. Annotation of the Anopheles gambiae and Drosophila melanogaster genomes has revealed the full extent of this enzyme family in insects. This mini review describes the insect GST enzyme family, focusing specifically on their role in conferring insecticide resistance.
Aedes aegyptitransferrin. Gene structure, expression pattern, and regulation
Authors: Harizanova N. , Georgieva T. , Dunkov B. C. , Yoshiga T. , Law J. H.
Published: January 2005

Mosquitoes and all other insects so far examined have an abundant haemolymph transferrin (Tsf). The exact function of these proteins has not been determined, but they may be involved in iron transport, in oogenesis and in innate immune defence against parasites and pathogens. The Tsf gene ofAedes aegyptihas been cloned and sequenced. It contains a single small intron, which contrasts it to vertebrate Tsf genes that contain up to sixteen introns. The promoter region of the gene is rich in putative NF‐κB binding sites, which is consistent with the postulated role of Tsf in insect innate immunity. Tsf message levels are very low in embryos and early larvae, but high in late larvae, pupae and adults. Western blotting experiments revealed high levels of Tsf protein in pupae and adults. Late larvae and ovaries of blood‐fed mosquitoes have little intact protein, but two prominent proteolytic degradation products. These may represent biologically active peptides, as has been shown for other organisms. Tsf message is down‐regulated by inorganic iron in the diet or environment, but up‐regulated by a blood meal in the adult female. The up‐regulation following a blood meal may, in part, be due to the decrease in juvenile hormone (JH) that is known to follow blood feeding. Treatment of blood‐fed females with methoprene, an analogue of JH, resulted in decrease of the Tsf message.
Molecular cloning and transcriptional activation of lysozyme‐encoding cDNAs in the mosquito Aedes aegypti
Authors: Ursic Bedoya R. J. , Mitzey A. M. , Obraztsova M. , Lowenberger C.
Published: January 2005

Lysozymes are enzymes characterized by their ability to break down bacterial cell walls. In insects certain lysozymes are only found in the midgut, whereas others are only found in the haemolymph and fat body after immune challenge. We identified two lysozyme‐encoding cDNAs from Aedes aegypti. Both deduced protein sequences are basic in nature, contain 148 amino acids including eight highly conserved cysteine residues, and their genomic sequences contain a single intron. Transcriptional profiles indicated that the predominant form is constitutively expressed and up‐regulated upon immune challenge and blood feeding in adult mosquitoes. The second form is expressed during early developmental stages, larvae and pupae, and at low levels in adults after immune challenge. Lysozymes in Aedes aegypti play both roles, defined by the spatial and temporal regulation of their expression.
Expression of Cyp6g1 and Cyp12d1 in DDT resistant and susceptible strains of Drosophila melanogaster
Authors: Festucci‐Buselli R. A. , Carvalho‐Dias A. S. , De Oliveira‐Andrade M. , Caixeta‐Nunes C. , Li H.‐M. , Stuart J. J. , Muir W. , Scharf M. E. , Pittendrigh B. R.
Published: January 2005

The Rst(2)DDT locus (loci) in Drosophila is associated with the over‐expression of two cytochrome P450 genes, Cyp6g1 and Cyp12d1. Using northern and western blot analysis we observed the expression pattern of these two genes in two DDT susceptible (Canton‐S and 91‐C) and three DDT resistant strains (Wisconsin, 91‐R and Hikone‐R). In Canton‐S and 91‐R, the CYP6G1 protein was constitutively expressed throughout development. In the Wisconsin strain, CYP6G1 was not expressed in third instar larvae unless the larvae are exposed to DDT. CYP12D1 protein was only expressed in adults. Cyp12d1 mRNA is induced in DDT resistant strains post‐exposure to DDT and the expression patterns of Cyp12d1 mRNA varied across DDT resistant strains. Our data support the hypothesis that there is evolutionary plasticity in the expression patterns of P450s associated with metabolic pesticide resistance.
Potential causes and life‐history consequences of sexual size dimorphism in mammals
Authors: ISAAC JOANNE L.
Published: January 2005

1. Male‐biased sexual size dimorphism (SSD) in mammals has been explained by sexual selection favouring large, competitive males. However, new research has identified other potential factors leading to SSD. The aim of this review is to evaluate current research on the causes of SSD in mammals and to investigate some consequences of SSD, including costs to the larger sex and sexual segregation.

2. While larger males appear to gain reproductive benefits from their size, studies have also identified alternative mating strategies, unexpected variance in mating success and found no clear relationship between degree of polygyny and dimorphism. This implies that sexual selection is unlikely to be the single selective force directing SSD.

3. Latitude seems to influence SSD primarily through variation in overall body size and seasonal food availability, which affect potential for polygyny. Likewise, population density influences resource availability and evidence suggests that food scarcity differentially constrains the growth of the sexes. Diverging growth patterns between the sexes appear to be the primary physiological mechanism leading to SSD.

4. Female‐biased dimorphism is most adequately explained by reduced male–male competition resulting in a decrease in male size. Female–female competition for dominance and resources, including mates, may also select for increased female size.

5. Most studies found that sexual segregation arises through asynchrony of activity budgets between the sexes. The larger sex can suffer sex‐biased mortality through increased parasite load, selective predation and the difficulty associated with sustaining a larger body size under conditions of resource scarcity.

6. None of the variables considered here appears to contribute a disproportionate amount to SSD in mammals. Several promising avenues of research are currently overlooked and long‐term studies, which have previously been biased toward ungulates, should be carried out on a variety of taxa.
The response of mammals to forest fire and timber harvest in the North American boreal forest
Authors: FISHER JASON T. , WILKINSON LISA
Published: January 2005

1. This paper reviews and compares the effects of forest fire and timber harvest on mammalian abundance and diversity, throughout successional time in the boreal forest of North America.

2. Temporal trends in mammal abundance and diversity are generally similar for both harvested and burned stands, with some differences occurring in the initiation stage (0–10 years post disturbance).

3. Small mammals and ungulates are most abundant immediately post disturbance, and decrease as stands age. Lynxes and hares utilize mid‐successional stands, but are rare in young and old stands. Bats, arboreal sciurids and mustelids increase in abundance with stand age, and are most abundant in old growth.

4. Substantial gaps in the data exist for carnivores; the response of these species to fire and harvest requires research, as predator–prey interactions can affect mammal community structure in both early and late successional stages.

5. The lack of explicit treatment of in‐stand forest structure post disturbance, in the reviewed literature made comparisons difficult. Where forest structure was considered, the presence of downed woody material, live residual trees and standing dead wood were shown to facilitate convergence of mammal communities to a pre‐disturbance state for both disturbance types.

6. Mammalian assemblages differed considerably between successional stages, emphasizing the importance of maintaining stands of each successional stage on the landscape when implementing forest management strategies.
Population status, trends and a re‐examination of the hypotheses explaining the recent declines of the southern elephant seal Mirounga leonina
Authors: MCMAHON CLIVE R. , BESTER MARTHÁN N. , BURTON HARRY R. , HINDELL MARK A. , BRADSHAW COREY J. A.
Published: January 2005

1. Between the 1950s and 1990s the southern elephant seal Mirounga leonina underwent large decreases in population size throughout most of its breeding range in the Southern Ocean. While current population estimates suggest a recent recovery, some breeding populations have continued to decrease in recent years (Macquarie and Marion Islands), others have either remained stable (South Georgia, Kerguelen and Heard Island) or have increased (Peninsula Valdés, Argentina).

2. Intrinsic hypotheses for patterns of regional decline include factors that are affected by density‐dependent mechanisms: (i) paucity of males, (ii) population ‘overshoot’ and (iii) pandemic disease. Extrinsic hypotheses include (iv) predation, (v) competition with fisheries concerns, (vi) interspecific competition, (vii) environmental change and (viii) human disturbance. Of the eight hypotheses proposed and examined here, we conclude that three can be discounted (i, v, viii), three are unlikely, but may require more testing (ii, iii, iv) and two are plausible (vi, vii).

3. The interspecific competition hypothesis is difficult to test because it requires the simultaneous monitoring of species that overlap directly with elephant seals, many of which have not been identified or little is known. However, an analysis of the relationship between log variance and log abundance (Taylor's power law) for populations of southern and northern elephant seals suggests that interspecific competition is not a significant factor in the decline of the southern elephant seal.

4. The hypothesis that decreases in southern elephant seal populations between the 1950s and 1990s were caused by the environmental change is the easiest to test and most plausible of the hypotheses. We propose a framework by which to test this hypothesis to determine how food availability affects individual survival.
A quantitative analysis of the abundance and demography of European hares Lepus europaeus in relation to habitat type, intensity of agriculture and climate
Authors: SMITH REBECCA K. , VAUGHAN JENNINGS NANCY , HARRIS STEPHEN
Published: January 2005

1. European hares Lepus europaeus have declined throughout Europe since the 1960s. Possible reasons for this include agricultural intensification and changes in climate and predator numbers, but no clear consensus has been reached as to the relative importance of each of these. We aimed to identify factors associated with high and low hare numbers throughout Europe, to determine which could have caused population declines.

2. Results of 77 research papers from 12 European countries were summarized. Relationships between hare density and demographics and habitat, climate, hunting and predator variables were examined and quantified where possible. Temporal changes in factors identified as being associated with high or low numbers of hares were then examined to see if they could explain population declines.

3. Data from pastural habitats were limited, but densities of hares were low. Arable habitats had higher densities than mixed areas in spring, unless farming was intensive in which case densities were similar. In autumn the two habitats had similar densities. Field size, temperature, precipitation and hunting had no effect on density throughout Europe. Fecundity was affected by climate.

4. Arable land, various crops, fallow habitat and temperature were positively associated, and monoculture, precipitation and predators negatively associated with hare abundance. The relationship of field size, pasture and woodland with abundance depended on spatial scale.

5. Habitat changes caused by agricultural intensification are the ultimate cause of hare population declines. Effects of changes in climate or predator numbers are magnified by the loss of high‐quality year‐round forage and cover. Further research is required on how habitat changes affect fecundity and survival, and to identify which parameters have the greatest impact on population numbers. Farmland management policies that target the re‐establishment of some of the habitat diversity lost within fields, farms and landscapes will help to reverse the decline of the European hare.
INVITED REVIEW: Quantitative trait locus mapping in natural populations: progress, caveats and future directions
Authors: SLATE JON
Published: January 2005

Over the last 15 years quantitative trait locus (QTL) mapping has become a popular method for understanding the genetic basis of continuous variation in a variety of systems. For example, the technique is now an integral tool in medical genetics, livestock production, plant breeding and population genetics of model organisms. Ten years ago, it was suggested that the method could be used to understand continuous variation in natural populations. In this review I: (i) clarify what is meant by natural population in the QTL context, (ii) discuss whether evolutionary biologists have successfully mapped QTL in natural populations, (iii) highlight some of the questions that have been addressed by QTL mapping in natural populations, (iv) describe how QTL mapping can be conducted in unmanipulated natural populations, (v) highlight some of the limitations of QTL mapping and (vi) try to predict some future directions for QTL mapping in natural populations.
INVITED REVIEW: Local adaptation and species segregation in two mussel (Mytilus edulis × Mytilus trossulus) hybrid zones
Authors: RIGINOS C. , CUNNINGHAM C. W.
Published: January 2005

Few marine hybrid zones have been studied extensively, the major exception being the hybrid zone between the mussels Mytilus edulis and Mytilus galloprovincialis in southwestern Europe. Here, we focus on two less studied hybrid zones that also involve Mytilus spp.; Mytilus edulis and Mytilus trossulus are sympatric and hybridize on both western and eastern coasts of the Atlantic Ocean. We review the dynamics of hybridization in these two hybrid zones and evaluate the role of local adaptation for maintaining species boundaries. In Scandinavia, hybridization and gene introgression is so extensive that no individuals with pure M. trossulus genotypes have been found. However, M. trossulus alleles are maintained at high frequencies in the extremely low salinity Baltic Sea for some allozyme genes. A synthesis of reciprocal transplantation experiments between different salinity regimes shows that unlinked Gpi and Pgm alleles change frequency following transplantation, such that post‐transplantation allelic composition resembles native populations found in the same salinity. These experiments provide strong evidence for salinity adaptation at Gpi and Pgm (or genes linked to them). In the Canadian Maritimes, pure M. edulis and M. trossulus individuals are abundant, and limited data suggest that M. edulis predominates in low salinity and sheltered conditions, whereas M. trossulus are more abundant on the wave‐exposed open coasts. We suggest that these conflicting patterns of species segregation are, in part, caused by local adaptation of Scandinavian M. trossulus to the extremely low salinity Baltic Sea environment.
FAST‐TRACK: Integrating QTL mapping and genome scans towards the characterization of candidate loci under parallel selection in the lake whitefish (Coregonus clupeaformis)
Authors: ROGERS S. M. , BERNATCHEZ L.
Published: January 2005

As natural selection must act on underlying genetic variation, discovering the number and location of loci under the influence of selection is imperative towards understanding adaptive divergence in evolving populations. Studies employing genome scans have hypothesized that the action of divergent selection should reduce gene flow at the genomic locations implicated in adaptation and speciation among natural populations, yet once ‘outlier’ patterns of variation have been identified the function and role of such loci needs to be confirmed. We integrated adaptive QTL mapping and genomic scans among diverging sympatric pairs of the lake whitefish (Coregonus clupeaformis) species complex in order to test the hypothesis that differentiation between dwarf and normal ecotypes at growth‐associated QTL was maintained by directional selection. We found evidence of significantly high levels of molecular divergence among eight growth QTL where two of the strongest candidate loci under the influence of directional selection exhibited parallel reductions of gene flow over multiple populations.
Nonshivering thermogenesis capacity associated to mitochondrial DNA haplotypes and gender in the greater white‐toothed shrew, Crocidura russula
Authors: FONTANILLAS PIERRE , DÉPRAZ ALINE , GIORGI MAUD S. , PERRIN NICOLAS
Published: January 2005

A selection gradient was recently suggested as one possible cause for a clinal distribution of mitochondrial DNA (mtDNA) haplotypes along an altitudinal transect in the greater white‐toothed shrew, Crocidura russula (Ehinger et al. 2002). One mtDNA haplotype (H1) rare in lowland, became widespread when approaching the altitudinal margin of the distribution. As H1 differs from the main lowland haplotype by several nonsynonymous mutations (including on ATP6), and as mitochondria play a crucial role in metabolism and thermogenesis, distribution patterns might stem from differences in the thermogenic capacity of different mtDNA haplotypes.

 In order to test this hypothesis, we measured the nonshivering thermogenesis (NST) associated with different mtDNA haplotypes. Sixty‐two shrews, half of which had the H1 haplotype, were acclimated in November at semioutdoor conditions and measured for NST throughout winter. Our results showed the crucial role of NST for winter survival in C. russula. The individuals that survived winter displayed a higher significant increase in NST during acclimation, associated with a significant gain in body mass, presumably from brown fat accumulation. The NST capacity (ratio of NST to basal metabolic rate) was exceptionally high for such a small species. NST was significantly affected by a gender × haplotype interaction after winter‐acclimation: females bearing the H1 haplotype displayed a better thermogenesis at the onset of the breeding season, while the reverse was true for males. Altogether, our results suggest a sexually antagonistic cyto‐nuclear selection on thermogenesis.
Population structure in African Drosophila melanogaster revealed by microsatellite analysis
Authors: DIERINGER DANIEL , NOLTE VIOLA , SCHLÖTTERER CHRISTIAN
Published: January 2005

Tropical sub‐Saharan regions are considered to be the geographical origin of Drosophila melanogaster. Starting from there, the species colonized the rest of the world after the last glaciation about 10 000 years ago. Consistent with this demographic scenario, African populations have been shown to harbour higher levels of microsatellite and sequence variation than cosmopolitan populations. Nevertheless, limited information is available on the genetic structure of African populations. We used X chromosomal microsatellite variation to study the population structure of D. melanogaster populations using 13 sampling sites in North, West and East Africa. These populations were compared to six European and one North American population. Significant population structure was found among African D. melanogaster populations. Using a Bayesian method for inferring population structure we detected two distinct groups of populations among African D. melanogaster. Interestingly, the comparison to cosmopolitan D. melanogaster populations indicated that one of the divergent African groups is closely related to cosmopolitan flies. Low, but significant levels of differentiation were observed for sub‐Saharan D. melanogaster populations from West and East Africa.
Chloroplast DNA variation of Quercus rubra L. in North America and comparison with other Fagaceae
Authors: MAGNI C. R. , DUCOUSSO A. , CARON H. , PETIT R. J. , KREMER A.
Published: January 2005

Quercus rubra is one of the most important timber and ornamental tree species from eastern North America. It is a widespread species growing under variable ecological conditions. Chloroplast DNA variation was studied by PCR‐RFLP (polymerase chain reaction‐restriction fragment length polymorphism) in 290 individuals from 66 populations sampled throughout the natural range. A total of 12 haplotypes were detected, with one found in 75% of the trees. Population differentiation is relatively low (GST = 0.46), even when similarities between haplotypes are taken into account (NST = 0.50), pointing to a weak phylogeographical structure. Furthermore, no spatial structure of genetic diversity could be detected. The genetic differentiation increased northwards, reflecting the postglacial history of Q. rubra. The unusual aspect of this study was the low level of chloroplast DNA genetic differentiation in Q. rubra compared to that typically observed in other oak species. Palynological evidence indicates that during the last glacial maximum, Q. rubra had one major distribution range with populations located relatively far to the north, resulting in only modest movement northwards when climate improved, whereas European white oaks were largely restricted to the southern European peninsulas and experienced extensive movements during the postglacial period. The contrasted geographical features and levels of tree species richness of both continents might further explain why congeneric species sharing similar life history traits have genetic structures that are so different.
Similarity coefficients for molecular markers in studies of genetic relationships between individuals for haploid, diploid, and polyploid species
Authors: KOSMAN E. , LEONARD K. J.
Published: January 2005

Determining true genetic dissimilarity between individuals is an important and decisive point for clustering and analysing diversity within and among populations, because different dissimilarity indices may yield conflicting outcomes. We show that there are no acceptable universal approaches to assessing the dissimilarity between individuals with molecular markers. Different measures are relevant to dominant and codominant DNA markers depending on the ploidy of organisms. The Dice coefficient is the suitable measure for haploids with codominant markers and it can be applied directly to (0,1)‐vectors representing banding profiles of individuals. None of the common measures, Dice, Jaccard, simple mismatch coefficient (or the squared Euclidean distance), is appropriate for diploids with codominant markers. By transforming multiallelic banding patterns at each locus into the corresponding homozygous or heterozygous states, a new measure of dissimilarity within locus was developed and expanded to assess dissimilarity between multilocus states of two individuals by averaging across all codominant loci tested. There is no rigorous well‐founded solution in the case of dominant markers. The simple mismatch coefficient is the most suitable measure of dissimilarity between banding patterns of closely related haploid forms. For distantly related haploid individuals, the Jaccard dissimilarity is recommended. In general, no suitable method for measuring genetic dissimilarity between diploids with dominant markers can be proposed. Banding patterns of diploids with dominant markers and polyploids with codominant markers represent individuals’ phenotypes rather than genotypes. All dissimilarity measures proposed and developed herein are metrics.
Genetic variation and phylogeographic analyses of two species of Carpobrotus and their hybrids in California
Authors: SCHIERENBECK KRISTINA A. , SYMONDS V. VAUGHAN , GALLAGHER KELLY G. , BELL JEFFREY
Published: January 2005

Despite the commonality and study of hybridization in plants, there are few studies between invasive and noninvasive species that examine the genetic variability and gene flow of cytoplasmic DNA. We describe the phylogeographical structure of chloroplast DNA (cpDNA) variation within and among several interspecific populations of the putative native, Carpobrotus chilensis and the introduced, Carpobrotus edulis (Aizoaceae). These species co‐occur throughout much of coastal California and form several ‘geographical hybrid populations’. Two hundred and thirty‐seven individuals were analysed for variation in an approximate 7.0 kb region of the chloroplast genome using PCR‐RFLP (polymerase chain reaction – restriction fragment length polymorphism) data. Phylogenetic analyses and cpDNA population differentiation were conducted for all morphotypes. Historic geographical dispersion and the coefficient of ancestry of the haplotypes were determined using nested clade analyses. Two haplotypic groupings (I and II) were represented in C. chilensis and C. edulis, respectively. The variation in cpDNA data is in agreement with the previously reported allozyme and morphological data; this supports relatively limited variation and high population differentiation among C. chilensis and hybrids and more wide‐ranging variation in C. edulis and C. edulis populations backcrossed with C. chilensis. C. chilensis disproportionately contributes to the creation of hybrids with the direction of gene flow from C. chilensis into C. edulis. The cpDNA data support C. chilensis as the maternal contributor to the hybrid populations.
Intriguing asexual life in marginal populations of the brown seaweed Fucus vesiculosus
Authors: TATARENKOV A. , BERGSTRÖM L. , JÖNSSON R. B. , SERRÃO E. A. , KAUTSKY L. , JOHANNESSON K.
Published: January 2005

Reproduction of attached large brown algae is known to occur only by sexual zygotes. Using microsatellites we show evolution of asexual reproduction in the bladder wrack promoting population persistence in the brackish water Baltic Sea (< 6 psu). Here a dwarf morph of Fucus vesiculosus is dominated by a single clone but clonal reproduction is also present in the common form of the species. We describe a possible mechanism for vegetative reproduction of attached algae, and conclude that clonality plays an important role in persistence and dispersal of these marginal populations, in which sexual reproduction is impaired by low salinity.
Phylogeography of the Italian wall lizard, Podarcis sicula, as revealed by mitochondrial DNA sequences
Authors: PODNAR MARTINA , MAYER WERNER , TVRTKOVIĆ NIKOLA
Published: January 2005

In a phylogeographical survey of the Italian wall lizard, Podarcis sicula, DNA sequence variation along an 887‐bp segment of the cytochrome b gene was examined in 96 specimens from 86 localities covering the distribution range of the species. In addition, parts of the 12S rRNA and 16S rRNA genes from 12 selected specimens as representatives of more divergent cytochrome b haploclades were sequenced (together about 950 bp). Six phylogeographical main groups were found, three representing samples of the nominate subspecies Podarcis sicula sicula and closely related subspecies and the other three comprising Podarcis sicula campestris as well as all subspecies described from northern and eastern Adriatic islands. In southern Italy a population group with morphological characters of P. s. sicula but with the mitochondrial DNA features of P. s. campestris was detected indicating a probably recent hybridization zone. The present distribution patterns were interpreted as the consequence of natural events like retreats to glacial refuges and postglacial area expansions, but also as the results of multiple introductions by man.
Super‐infections ofWolbachiain byturid beetles and evidence for genetic transfer between A and B super‐groups ofWolbachia
Authors: MALLOCH G. , FENTON B.
Published: January 2005

Wolbachiaare maternally inherited bacteria responsible for altering host reproduction. The two main groups found in insects, A and B, are based on molecular characterization using ribosomal,ftsZ,wsp(Wolbachiasurface protein) orgroE genes. We have used thewspandftsZ genes to studyWolbachiain byturid beetles.Byturus affiniscontained a single copy of theftsZ gene which grouped with AftsZ sequences and a single copy of thewspgene which grouped with Bwspsequences. This suggests that genetic exchange between A and B groups has occurred in theWolbachiaof this beetle.FtsZ andwspsequences that were identical or nearly identical to those ofB. affiniswere found inB. tomentosus, suggesting that it also contains the same recombinantWolbachiagenotype. Most other byturids had more than onewspsequence with at least one from the A and B groups, suggesting multiple copies of bacterial genes or multiple infections.B. ochraceusandB. unicolorboth had four distinctwspgene sequences. All the byturids had a closely related Awspsequence and most a closely related Bwspsequence. Therefore, there appears to be an association between specific A and Bwsptypes.
Multilevel genetic analyses of two European supercolonies of the Argentine ant, Linepithema humile
Authors: JAQUIÉRY J. , VOGEL V. , KELLER L.
Published: January 2005

Some ants have an extraordinary unicolonial social organization, whereby individuals mix freely among physically separated nests. Recently, it was shown that the European population of Linepithema humile consisted of two enormous unicolonial supercolonies. Workers of the same supercolony are never aggressive to each other. In contrast, aggressiveness is invariably high between workers from different supercolonies. Here we investigated whether gene flow occurs between two supercolonies. We identified a contact zone in which we sampled 46 nests. For each nest, aggression tests were conducted against workers from reference nests from both supercolonies. Workers were always very aggressive towards workers of one of the supercolonies but not to workers of the other. Thus, all nests could be clearly assigned to one of the two supercolonies. For 22 of the 46 nests, we genotyped 15–16 workers at five microsatellite loci. A four‐level hierarchical analysis of variance revealed very strong genetic differentiation between the two supercolonies (FSUPERCOLONY‐TOTAL = 0.541) and low differentiation between sectors (i.e. group of nests connected together with trails) within supercolonies (FSECTOR‐SUPERCOLONY = 0.064). The very high differentiation between the two supercolonies indicates a lack of ongoing gene flow, a conclusion further bolstered by the finding that the two supercolonies share no common alleles at two of the five microsatellite loci. A Bayesian clustering method also revealed the occurrence of two distinct clusters. These clusters exactly match the grouping obtained by aggression tests. None of the 332 genotyped individuals were admixed despite the fact that some nests of the two supercolonies were separated by less than 30 m. These results demonstrate that the two supercolonies have completely separate gene pools.
SNPs in ecological and conservation studies: a test in the Scandinavian wolf population
Authors: SEDDON J. M. , PARKER H. G. , OSTRANDER E. A. , ELLEGREN H.
Published: January 2005

Single nucleotide polymorphisms (SNPs) have the potential to become the genetic marker of choice in studies of the ecology and conservation of natural populations because of their capacity to access variability across the genome. In this study, we provide one of the first demonstrations of SNP discovery in a wild population in order to address typical issues of importance in ecology and conservation in the recolonized Scandinavian and neighbouring Finnish wolfCanis lupuspopulations. Using end sequence from BAC (bacterial artificial chromosome) clones specific for dogs, we designed assays for 24 SNP loci, 20 sites of which had previously been shown to be polymorphic in domestic dogs and four sites were newly identified as polymorphic in wolves. Of the 24 assayed loci, 22 SNPs were found to be variable within the Scandinavian population and, importantly, these were able to distinguish individual wolves from one another (unbiased probability of identity of 4.33 × 10−8), providing equivalent results to that derived from 12 variable microsatellites genotyped in the same population. An assignment test shows differentiation between the Scandinavian and neighbouring Finnish wolf populations, although not all known immigrants are accurately identified. An exploration of the misclassification rates in the identification of relationships shows that neither 22 SNP nor 20 microsatellite loci are able to discriminate across single order relationships. Despite the remaining obstacle of SNP discovery in nonmodel organisms, the use of SNPs in ecological and conservation studies is encouraged by the advent of large scale screening methods. Furthermore, the ability to amplify extremely small fragments makes SNPs of particular use for population monitoring, where faecal and other noninvasive samples are routinely used.
Brood size modifications affect plumage bacterial assemblages of European starlings
Authors: LUCAS FRANÇOISE S. , MOUREAU BENOIT , JOURDIE VIOLAINE , HEEB PHILIPP
Published: January 2005

During reproduction, birds face trade‐offs between time and energy devoted to parental effort and traits associated with self‐maintenance. We manipulated brood sizes to investigate the effects of such trade‐offs on feather bacterial densities and the structure of bacterial assemblages on feathers in adult European starlings,Sturnus vulgaris, andin vitrofeather degradation. As predicted by a trade‐off between parental effort and self‐maintenance, we found that birds with enlarged broods had more free‐living bacteria on their feathers than birds with reduced broods. Furthermore, we found a significant interaction between brood manipulation and original brood size on free‐living bacterial densities suggesting that the trade‐off is mediated by the adults’ initial reproductive investment. In contrast, brood size manipulations had no significant effect on densities of attached bacteria. Using ribosomal intergenic spacer analysis (RISA), we demonstrated that brood manipulations significantly modified the structure (band pattern) of feather‐degrading bacterial assemblages, but had no significant effect on their richness (number of bands) or thein vitrofeather degradation.In vitrofeather degradation varied in relation to the premanipulation brood size and positively with the richness of the feather degrading bacterial community. Besides brood manipulation effect, we found that ecological factors and individual traits, such as the age, the nest location or the capture date, shaped bacterial assemblages and feather degradation capacities.
Male nest site fidelity and female serial polyandry in lingcod (Ophiodon elongatus, Hexagrammidae)
Authors: KING JACQUELYNNE R. , WITHLER RUTH E.
Published: January 2005

Nest site fidelity and serial polyandry were examined in lingcod, Ophiodon elongatus, a teleost fish in which the nest‐guarding male parent invests more heavily in parental care than the elusive female parent. Lingcod parental and progeny genotypes were established for fish spawning on a 200 m2 section of Snake Island reef, British Columbia in two successive years to evaluate male and female mate choice (monogamy or polygamy) and nest site reuse by the same parents (nest site fidelity) and/or different parents (nest site affinity). Thirteen nests (egg masses) guarded by nine males and 14 nests guarded by seven males were observed in 2002 and 2003, respectively. No female laid more than one nest per season or spawned in the study area in both years. In contrast, at least six (86%) and possibly all seven (100%) of the 2003 guardian males had been guardian or auxiliary males in 2002. Both nest site affinity and extreme male nest site fidelity were observed, with at least four males reusing the exact same nest site. Serial polyandry resulting from the high male and low female nest site fidelity is consistent with predictions based on a low female parental investment and high rate of progeny loss to predation and cannibalism. Male polygyny, achieved primarily by cuckoldry within seasons, was enhanced by the lack of female fidelity between seasons. Polygamy in both sexes of nest‐tending marine fish may minimize reproductive skew and maximize genetic diversity within populations.
Divergent trends in maternal cigarette smoking during pregnancy: United States 1990–99
Authors: Ananth Cande V. , Kirby Russell S. , Kinzler Wendy L.
Published: January 2005

While examination of causes for trends in smoking have largely focused on how changes have occurred with maternal age and, less commonly, time period, little is known as to how age, period and birth cohort interact on trends in the prevalence of smoking during pregnancy. We performed a population‐based, retrospective cohort study based on the vital statistics records comprised of White (n = 24 499 629) and Black (n = 5 096 625) women delivering in the United States in 1990–99. Smoking prevalence rates were derived by seven 5‐year maternal age groups (15–19 to 45–49 years), two time periods (1990–94 and 1995–99), and eight 5‐year maternal birth cohorts (1945–49 to 1980–84) after adjusting for the confounding effects of gravidity, education, marital status, and lack of prenatal care through multivariable logistic regression models. The prevalence of smoking was 17.3% among Whites, and 13.5% among Blacks, with substantial variations by age, time period, and birth cohort. The rate declined with increasing age among Whites during the 1990–94 and 1995–99 periods. Among Blacks, the rates increased steeply with advancing age up to 25–29 years and began to decline thereafter. Smoking rates declined among both Whites and Blacks with increasing birth cohort within each age strata. These rates were highest among multigravid women (gravida ≥ 2), and lowest among primigravid women. The rates among Whites declined with increasing maternal age for each gravida. Among Blacks, smoking rates for each gravida increased with advancing age up to 25–29 years, and plateaued among older women. Variation in smoking prevalence by age, time period, and birth cohort provides impetus for designing interventions to reduce smoking. Such studies should not only consider cross‐sectional trends, but also the divergent patterns by age and cohort among women of different race/ethnic groups and gravidity.
Early life influences on serum 1,25 (OH)2 vitamin D
Authors: Arden Nigel K. , Syddall Holly E. , Javaid Muhammad K. , Dennison Elaine M. , Swaminathan R. , Fall Caroline , Cooper Cyrus
Published: January 2005

There is increasing evidence to support the role of the intrauterine and early postnatal environment in determining adult bone mass and risk of fracture. The mechanisms by which this occurs are uncertain but include perturbations in several endocrine axes. Vitamin D is integrally involved in bone metabolism and is therefore an ideal candidate. This study assesses whether birthweight and weight at 1 year of age are associated with the calcium vitamin D axis in elderly women.

Vitamin D metabolites, parathyroid hormone, bone mineral density and biochemical markers of bone turnover were measured in 129 healthy women (mean age 65.5 years) from the MRC Hertfordshire Cohort Study whose birthweight and weight at 1 year were available from records.

Serum 1,25 (OH)2 vitamin D concentrations were reduced with increasing weight at 1 year (19.1% reduction between the lowest and highest tertiles, P < 0.01). A similar, but weaker trend was seen for birthweight. These associations were not explained by serum levels of serum calcium, phosphate, PTH, creatinine or sex hormones. The association of serum calcium with 1,25 (OH)2 vitamin D was greatest in the lowest tertile with little association in the highest tertile suggesting an increased sensitivity of renal 1‐α hydroxylase in the lowest tertile. Highest levels of 1,25 (OH)2 vitamin D were associated with low BMD and high levels of urinary N‐telopeptide suggesting that vitamin D metabolism may mediate the intrauterine and early postnatal environmental effects on adult BMD.