Search PubMed⌕ Search

Biomedical subjects

K L Buchanan

Publications and source records attributed to K L Buchanan.

At least 19 recordsLinked to original sources
PubMed2003

Song as an honest signal of past developmental stress in the European starling (Sturnus vulgaris).

Bird song is a sexually selected male trait where females select males on the basis of song quality. It has recently been suggested that the quality of the adult male song may be determined by nutritional stress during early development. Here, we test the 'nutritional-stress hypothesis' using the complex song of the European starling. Fledgling starlings were kept under experimental treatment (unpredictable short-term food deprivations) or control conditions (ad libitum food supply), for three months immediately after independence. We measured their physiological and immune responses during the treatment and recorded song production during the following spring. Birds in the experimental group showed increased mass during the treatment and also a significantly suppressed humoral response compared with birds in the control group. There was no difference between the groups in the cell-mediated response. Next spring, males in the experimental group spent less time singing, sang fewer song bouts, took longer to start singing and also sang significantly shorter song bouts. These data support the hypothesis that both the quality and quantity of song produced by individual birds reflect past developmental stress. The results also suggest the 'nutritional-stress hypothesis' is best considered as a more general 'developmental-stress hypothesis'.

Animal Nutritional Physiological Phenomena↗
PubMed2003

Song as an honest signal of developmental stress in the zebra finch (Taeniopygia guttata).

In a wide range of bird species, females have been shown to express active preferences for males that sing more complex songs. Current sexual selection theory predicts that for this signal to remain an honest indicator of male quality, it must be associated with an underlying cost of development or maintenance. There has been considerable debate questioning the costs associated with song production and learning. Recently, the nutritional stress hypothesis proposed that song complexity could act as an indicator of early developmental history, since the song control nuclei in the brain are laid down early in life. Here we test the nutritional stress hypothesis, by investigating the effects of dietary stress on the quality of adult song produced. In addition, we tested the effects of elevated corticosterone during development on song production to test its possible involvement in mediating the effects of developmental stress. The results demonstrate that both dietary restriction and elevated corticosterone levels significantly reduced nestling growth rates. In addition, we found that experimentally stressed birds developed songs with significantly shorter song motif duration and reduced complexity. These results provide novel experimental evidence that complex song repertoires may have evolved as honest signals of male quality, by indicating early developmental rearing conditions.

Adaptation, Physiological↗
PubMed2003

An illustration of variable precision rough set theory: the gender classification of the European barn swallow (Hirundo rustica).

This paper introduces a new technique in the investigation of object classification and illustrates the potential use of this technique for the analysis of a range of biological data, using avian morphometric data as an example. The nascent variable precision rough sets (VPRS) model is introduced and compared with the decision tree method ID3 (through a 'leave n out' approach), using the same dataset of morphometric measures of European barn swallows (Hirundo rustica) and assessing the accuracy of gender classification based on these measures. The results demonstrate that the VPRS model, allied with the use of a modern method of discretization of data, is comparable with the more traditional non-parametric ID3 decision tree method. We show that, particularly in small samples, the VPRS model can improve classification and to a lesser extent prediction aspects over ID3. Furthermore, through the 'leave n out' approach, some indication can be produced of the relative importance of the different morphometric measures used in this problem. In this case we suggest that VPRS has advantages over ID3, as it intelligently uses more of the morphometric data available for the data classification, whilst placing less emphasis on variables with low reliability. In biological terms, the results suggest that the gender of swallows can be determined with reasonable accuracy from morphometric data and highlight the most important variables in this process. We suggest that both analysis techniques are potentially useful for the analysis of a range of different types of biological datasets, and that VPRS in particular has potential for application to a range of biological circumstances.

Animals↗
PubMed2002

Mechanisms of bacterial pathogenicity.

Pathogenic bacteria utilise a number of mechanisms to cause disease in human hosts. Bacterial pathogens express a wide range of molecules that bind host cell targets to facilitate a variety of different host responses. The molecular strategies used by bacteria to interact with the host can be unique to specific pathogens or conserved across several different species. A key to fighting bacterial disease is the identification and characterisation of all these different strategies. The availability of complete genome sequences for several bacterial pathogens coupled with bioinformatics will lead to significant advances toward this goal.

Adhesins, Bacterial↗
PubMed2001

DNA methyltransferase 3B mutations linked to the ICF syndrome cause dysregulation of lymphogenesis genes.

ICF (immunodeficiency, centromeric region instability and facial anomalies) is a recessive disease caused by mutations in the DNA methyltransferase 3B gene (DNMT3B). Patients have immunodeficiency, chromosome 1 (Chr1) and Chr16 pericentromeric anomalies in mitogen-stimulated lymphocytes, a small decrease in overall genomic 5-methylcytosine levels and much hypomethylation of Chr1 and Chr16 juxtacentromeric heterochromatin. Microarray expression analysis was done on B-cell lymphoblastoid cell lines (LCLs) from ICF patients with diverse DNMT3B mutations and on control LCLs using oligonucleotide arrays for approximately 5600 different genes, 510 of which showed a lymphoid lineage-restricted expression pattern among several different lineages tested. A set of 32 genes had consistent and significant ICF-specific changes in RNA levels. Half of these genes play a role in immune function. ICF-specific increases in immunoglobulin (Ig) heavy constant mu and delta RNA and cell surface IgM and IgD and decreases in Ig(gamma) and Ig(alpha) RNA and surface IgG and IgA indicate inhibition of the later steps of lymphocyte maturation. ICF-specific increases were seen in RNA for RGS1, a B-cell specific inhibitor of G-protein signaling implicated in negative regulation of B-cell migration, and in RNA for the pro-apoptotic protein kinase C eta gene. ICF-associated decreases were observed in RNAs encoding proteins involved in activation, migration or survival of lymphoid cells, namely, transcription factor negative regulator ID3, the enhancer-binding MEF2C, the iron regulatory transferrin receptor, integrin beta7, the stress protein heme oxygenase and the lymphocyte-specific tumor necrosis factor receptor family members 7 and 17. No differences in promoter methylation were seen between ICF and normal LCLs for three ICF upregulated genes and one downregulated gene by a quantitative methylation assay [combined bisulfite restriction analysis (COBRA)]. Our data suggest that DNMT3B mutations in the ICF syndrome cause lymphogenesis-associated gene dysregulation by indirect effects on gene expression that interfere with normal lymphocyte signaling, maturation and migration.

Cell Line↗
PubMed2001

Testosterone influences basal metabolic rate in male house sparrows: a new cost of dominance signalling?

Sexually selected signals of individual dominance have profound effects on access to resources, mate choice and gene flow. However, why such signals should honestly reflect individual quality is poorly understood. Many such signals are known to develop under the influence of testosterone. We conducted an experiment in male house sparrows in which testosterone was manipulated independently during two periods: before the onset of the breeding season and prior to the autumn moult. We then measured the effects of these manipulations on basal metabolic rate and on the size of the chest bib, a sexually selected signal. The results demonstrate that testosterone simultaneously affects both signal development and basal metabolic rate in the house sparrow (Passer domesticus). This evidence, therefore, supports a novel conclusion: that testosterone-dependent signals act as honest indicators of male quality possibly because only high-quality individuals can sustain the energetic costs associated with signal development.

Animals↗
PubMed2001

Three-dimensional tissue assemblies: novel models for the study of Salmonella enterica serovar Typhimurium pathogenesis.

The lack of readily available experimental systems has limited knowledge pertaining to the development of Salmonella-induced gastroenteritis and diarrheal disease in humans. We used a novel low-shear stress cell culture system developed at the National Aeronautics and Space Administration in conjunction with cultivation of three-dimensional (3-D) aggregates of human intestinal tissue to study the infectivity of Salmonella enterica serovar Typhimurium for human intestinal epithelium. Immunohistochemical characterization and microscopic analysis of 3-D aggregates of the human intestinal epithelial cell line Int-407 revealed that the 3-D cells more accurately modeled human in vivo differentiated tissues than did conventional monolayer cultures of the same cells. Results from infectivity studies showed that Salmonella established infection of the 3-D cells in a much different manner than that observed for monolayers. Following the same time course of infection with Salmonella, 3-D Int-407 cells displayed minimal loss of structural integrity compared to that of Int-407 monolayers. Furthermore, Salmonella exhibited significantly lower abilities to adhere to, invade, and induce apoptosis of 3-D Int-407 cells than it did for infected Int-407 monolayers. Analysis of cytokine expression profiles of 3-D Int-407 cells and monolayers following infection with Salmonella revealed significant differences in expression of interleukin 1alpha (IL-1alpha), IL-1beta, IL-6, IL-1Ra, and tumor necrosis factor alpha mRNAs between the two cultures. In addition, uninfected 3-D Int-407 cells constitutively expressed higher levels of transforming growth factor beta1 mRNA and prostaglandin E2 than did uninfected Int-407 monolayers. By more accurately modeling many aspects of human in vivo tissues, the 3-D intestinal cell model generated in this study offers a novel approach for studying microbial infectivity from the perspective of the host-pathogen interaction.

Apoptosis↗
PubMed2000

An upstream Oct-1- and Oct-2-binding silencer governs B29 (Ig beta) gene expression.

The B cell-specific B29 (Igbeta) gene is activated in the earliest B cell precursors and is expressed throughout B cell development. Tissue-specific expression of the murine B29 gene is controlled by a B cell-specific promoter whose activity is governed by a cassette of upstream transcriptional silencers. This study describes a potent new silencer that is located 5' of the previously identified B29 silencer elements, FROG and TOAD. Like these known elements, the new B29 silencer is not restricted to the B29 promoter. Nuclear proteins from all cell lines tested interacted with this A+T-rich sequence, which closely resembled a noncanonical octamer binding motif and also conformed to the consensus sequence for nuclear matrix attachment regions. Interaction of Oct-1 and Oct-2 with the B29 A+T-rich sequence was confirmed using octamer-specific Abs. Oct-1/Oct-2 binding was required for the inhibitory activity of this sequence because mutations that blocked Oct-1/Oct-2 binding also eliminated inhibition of the B29 promoter. This B29 A+T-rich sequence specifically interacted with isolated nuclear matrix proteins in vitro, suggesting that it may also function as a matrix attachment region element. Maintenance of the level of B29 gene expression through the interaction of the minimal promoter and the upstream silencer elements FROG, TOAD, and the A+T-rich Oct-1/Oct-2 binding motif may be essential for normal B cell development and/or function.

5' Untranslated Regions↗
PubMed2000

Song as an indicator of male parental effort in the sedge warbler.

Repertoire size has been found to be a sexually selected trait in a number of bird species, although the advantages of mating with a male who possesses a complex song remain unclear. We studied the potential role of song as an indicator of male parental effort in the sedge warbler Acrocephalus schoenobaenus. The male provisioning rate was used as a measure of male parental effort and was found to increase with nestling age and brood size. When controlling for chick age, brood size and other variables, we found a highly significant positive correlation between a measure of song complexity (repertoire size) and male parental effort. Both male parental effort and repertoire size were found to be positively correlated with chick weight when controlling for chick age. We found no correlation between a measure of song output (amount of song flighting) or territory size and parental effort. Repertoire size is known to be the most important cue in female choice amongst sedge warblers and we discuss the possible reasons for this. We suggest that, in choosing a male with a large repertoire, a female obtains not only indirect benefits but also direct benefits in the form of increased parental effort.

Animals↗
PubMed2000

Requirement for CD4(+) T lymphocytes in host resistance against Cryptococcus neoformans in the central nervous system of immunized mice.

The importance of cell-mediated immunity (CMI) and CD4(+) T lymphocytes in host resistance against Cryptococcus neoformans is well documented and is exemplified by the high susceptibility to progressive infection with this pathogen of AIDS patients with reduced CD4(+) T-cell numbers. Although much has been learned about the role of CMI in the clearance of C. neoformans from the lungs and other internal organs, less is known about the protective mechanisms in the brain, the organ most frequently involved with a fatal outcome of cryptococcosis. We hypothesized that host resistance mechanisms against C. neoformans in the central nervous system (CNS) were similar to those outside the CNS (i.e., gamma interferon [IFN-gamma], CD4(+) T cells, and others). To test this hypothesis, we used a murine model of cryptococcal meningitis whereby cryptococci are introduced directly into the CNS. In experiments where mice were immunized to mount an anticryptococcal CMI response, our results indicate that immunization induced protective mechanisms that could be detected in the CNS by inhibition of the growth of viable yeast cells. Flow cytometric analyses of leukocytes in brain and spinal cord homogenates revealed that T lymphocytes, macrophages, and neutrophils accumulated in C. neoformans-infected brains of immune mice. In vivo depletion of CD4(+) T cells, but not CD8(+) T cells, resulted in significantly reduced leukocyte accumulation in the brains of immune mice. Furthermore, depletion of CD4(+) T cells or neutralization of IFN-gamma exacerbated CNS infection in immune mice, suggesting a critical role for CMI mechanisms in acquired protection in the CNS.

Animals↗
PubMed2000

Song, sexual selection, and a song control nucleus (HVc) in the brains of European sedge warblers.

Female sedge warblers select males that have more complex songs as mates. This study tests two predictions concerning HVc, a telencephalic nucleus that is essential for song learning and production: first, that males with more complex songs will have a larger HVc, and second that males who pair successfully will have a larger HVc than unpaired males. Data on song composition and pairing status were collected from wild sedge warblers breeding in Hungary. We found significant positive correlations between three song attributes (repertoire size, song complexity, and song length) and the size of HVc. Males that paired successfully also had more complex songs (repertoire size and song complexity, though not song length) than males that did not. However, we find no direct evidence that males who paired successfully had a larger HVc than unpaired males. These findings are discussed in relation to the possible functions of HVc and also to current views on sexual selection and the evolution of the song control pathway.

Animal Communication↗
PubMed1999

Pathogenesis of Cryptococcus neoformans is associated with quantitative differences in multiple virulence factors.

Two isolates of Cryptococcus neoformans were previously described as being highly divergent in their level of capsule synthesis in vivo and in their virulence for mice. The highly virulent isolate (NU-2) produced more capsule than a weakly virulent isolate (184A) in vitro under tissue culture conditions and in vivo. This investigation was done to determine if there were differences between the two isolates in other factors that might also contribute to virulence. Growth rate was not a factor as NU-2 grew more slowly than 184A. Based on PCR fingerprinting the two isolates were genetically different providing an opportunity to examine differences in multiple virulence traits. Quantitative analysis revealed that NU-2 expressed significantly more melanin and mannitol than did 184A. Although the isolates expressed the same capsular chemotype, NU-2 produced an additional structure reporter group (SRG) under tissue culture conditions that was not present when grown in glucose salts/urea/basal medium (GSU). Capsular polysaccharide SRGs of 184A were unaffected by shifting the growth conditions from GSU to tissue culture conditions. Our results suggest that pathogenesis of a C. neoformans strain is dictated by the quantitative expression of the strain's combined virulence traits. Regulators of the expression of these genes may be playing key roles in virulence.

Chromatography, Gas↗
PubMed1999

Differential regulation of immune responses by highly and weakly virulent Cryptococcus neoformans isolates.

Early inflammatory responses, delayed-type hypersensitivity (DTH) responses, and cytokine profiles were studied in mice infected by the pulmonary route with either a highly virulent isolate (NU-2) or a weakly virulent isolate (184A) of Cryptococcus neoformans. After infection, NU-2 remained in the lungs and the capsule became more pronounced during the first 24 h, whereas 184A induced an immediate inflammatory reaction and was rapidly cleared from the lungs. Cryptococcal antigen (GXM) appeared in sera early after infection with NU-2 and increased over the entire observation period. There was no detectable GXM in sera from 184A-infected mice. Both C. neoformans isolates induced anticryptococcal cell-mediated immune responses, but the responses had different profiles. DTH in NU-2-infected mice appeared at day 15 after infection and waned by day 21, whereas DTH in 184A-infected mice was present by day 5 and continued to increase. T helper 1 (Th1) cytokines (interleukin 2 [IL-2] and gamma interferon) were made by spleen cells early after infection with either isolate. NU-2-infected mice lost their ability to produce these cytokines, but 184A-infected mice retained it. IL-4, a Th2 cytokine, was not detected in infected mice. The regulatory cytokine IL-10 was made by spleen cells early but not later after infection with the highly virulent isolate and was not produced by spleen cells from 184A-infected mice. IL-10-deficient mice survived an NU-2 infection significantly longer than wild-type mice, suggesting that IL-10 is important in down-regulating the protective immune response. The induction of anergy appears to be responsible for the inability of NU-2-infected mice to control a C. neoformans infection.

Acute-Phase Reaction↗
PubMed1998

Expression of bright at two distinct stages of B lymphocyte development.

The B cell regulator of Ig heavy chain transcription (Bright) is a DNA-binding protein that was originally discovered in a mature Ag-specific B cell line after stimulation with IL-5 and Ag. It binds to the intronic heavy chain enhancer and 5' of the V1 S107 family V(H) promoter. Several studies suggested that Bright may increase transcription of the heavy chain locus, and expression in cell lines was limited to those representing mature B cells. We have now analyzed normal hemopoietic tissues for the expression of Bright during B lymphocyte differentiation. We expected to find Bright expression in a subset of mature spleen cells, but also observed Bright in a subset of normal B lymphocytic progenitors in both adult bone marrow (BM) and in fetal liver as early as day 12 of gestation. Bright was also expressed in the small percentage of CD4(low) cells in the thymus that are newly arrived from the BM and are not yet committed to the T lymphocyte lineage, but was not observed at later stages of T cell differentiation in either the spleen or thymus. Bright mRNA was not detected in the immature B lymphocytes that initially populate the spleen after migration from the BM. In addition, new splice variants of Bright were observed in fetal tissues. Thus, Bright expression is highly regulated in normal murine lymphocytes and occurs both early and late during B cell differentiation. These findings may have important implications for the function of Bright in regulating Ig transcription.

Animals↗
PubMed1997

Family-specific differences in transcription efficiency of Ig heavy chain promoters.

Murine Ig variable region heavy chain genes (V(H)) are grouped into families based on coding sequence homology. We observed that the accompanying promoter sequences were also conserved in a family-specific manner. Remarkably, no one has directly compared the transcription efficiencies of V(H) genes from different families. Using an in vitro transcription system, we found that transcription efficiencies of different V(H) promoters differed by as much as 70-fold. These differences could be attributed to variation in the octamer-heptamer and TATA sequences, as well as to the presence or absence of initiator elements. The J558 family promoter exhibited the highest level of transcription and specifically interacted with an Oct-1 dimer not bound by other V(H) promoters. These data suggest that differential transcription and regulation of V(H) promoters could occur in vivo. The increased transcription efficiency of the J558 promoter relative to other V(H) promoters also presents a possible explanation for the abundance of J558 sterile transcripts observed before V(H)DJ(H) rearrangement.

Animals↗
PubMed1997

Reassessment of germline heavy chain transcripts from two murine VH families.

While expression of functional heavy chain immunoglobulin mRNA requires rearrangement of variable (VH), diversity (D) and (JH) gene segments, these individual gene segments can be transcribed prior to their rearrangement. It has been proposed that the resulting germline, or sterile, transcripts play an important role in the rearrangement process because strong correlations between rearrangement frequency and sterile transcript levels have been observed in some studies. Murine VH genes have been grouped into families on the basis of coding sequence homology. VH families rearrange in a developmentally regulated manner, so that rearrangements of genes from several VH families are detected earlier than rearrangements of J558 family genes. Paradoxically, the only VH family for which sterile transcripts have been documented is the J558 family. We used RT-PCR analyses to ask whether sterile transcripts from other VH families could be detected in fetal liver samples prior to their rearrangement. While J558 family germline transcripts were easily detected, no sterile transcripts were observed from the S107 family. Our studies also revealed the ability of small quantities of degraded genomic DNA to nonspecifically prime cDNA synthesis, emphasizing the need for caution in interpreting RT-PCR data in which family-specific oligos are used for cDNA production. These results cast doubt on the idea that sterile transcripts are required for V(H)DJ(H) rearrangement.

Animals↗
PubMed1997

Kinetics of cellular infiltration and cytokine production during the efferent phase of a delayed-type hypersensitivity reaction.

Cell-mediated immunity is a primary host resistance mechanism against many infectious organisms and is responsible for leucocyte recruitment to the infection site. Delayed-type hypersensitivity (DTH) reactions are in vivo correlates of cell-mediated immunity and have long been used to assess the level of cell-mediated immune (CMI) responsiveness to specific antigens. It has been difficult to study the kinetics of cellular influx and cytokine composition at the site of an on-going CMI reaction. Consequently, knowledge of the sequential events occurring during the efferent phase of a CMI response is incomplete. Here we report on the use of a gelatin sponge model for evaluating the progression of events during the effector phase of a DTH reaction to antigens of the mycotic organism Cryptococcus neoformans. Previously, we have shown that 24 hr after antigen injection into sponges in infected or immune mice, the leucocyte types infiltrating the sponges are consistent with a classical murine DTH reaction. Through kinetic studies, we show here that neutrophils are the first leucocytes to appear in DTH-reactive sponges, followed by increases in lymphocyte and then monocyte numbers. Tumour necrosis factor (TNF), interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and IL-5 were elevated in DTH-reactive sponges compared with control sponges, and each cytokine had a relatively unique temporal profile. IL-4 was not detectable in the sponges. Together our data indicate that the expression of a CMI response comprises a well-regulated sequential influx of leucocytes that contribute to the lymphokine composition of the reaction.

Animals↗