William Turner's lectures on the comparative anatomy of the placenta.
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Anatomy, Comparative↗
Biomedical subjects
D Haig
Publications and source records attributed to D Haig.
Gestational drive and the green-bearded placenta.
A "green beard" refers to a gene, or group of genes, that is able to recognize itself in other individuals and direct benefits to these individuals. Green-beard effects have been dismissed as implausible by authors who have implicitly assumed sophisticated mechanisms of perception and complex behavioral responses. However, many simple mechanisms for genes to "recognize" themselves exist at the maternal-fetal interface of viviparous organisms. Homophilic cell adhesion molecules, for example, are able to interact with copies of themselves on other cells. Thus, the necessary components of a green-beard effect -- feature, recognition, and response -- can be different aspects of the phenotype of a single gene. Other green-beard effects could involve coalitions of genes at closely linked loci. In fact, any form of epistasis between a locus expressed in a mother and a closely linked locus expressed in the fetus has the property of "self-recognition." Green-beard effects have many formal similarities to systems of meiotic drive and, like them, can be a source of intragenomic conflict.
Cell Adhesion↗
Do imprinted genes have few and small introns?
A gene is described as imprinted if its pattern of expression depends on whether it passed the previous generation in a male or female germ line. A recent paper reports that imprinted genes have fewer and smaller introns than a control set of genes. The differences are striking but their interpretation is unclear. The loss of introns after a gene becomes imprinted is not sufficient to explain why imprinted genes have fewer introns than average, because related unimprinted genes also have few introns. Similarly, small introns appear to be a property of chromosomal region rather than of imprinting status itself, because neighboring unimprinted genes also have small introns.
Animals↗
Cytokines and their inhibitors in orf virus infection.
The epitheliotropic parapoxvirus, orf virus, can repeatedly infect sheep skin. A specific immune response is generated as reinfections induce smaller lesions with quicker resolution times than primary lesions. Cyclosporin-A treatment abrogates this partial immunity. Cytokine mRNAs detected in lesion biopsies include the transcripts for IL-1 beta, IL-3 GM-CSF, TNF-alpha and, less reproducibly, IFN-gamma. CD4+ T-cells predominate in afferent lymph draining the site of infection, and are the major source of GM-CSF and IFN-gamma. IL-1 beta and IL-8 are also detected. The orf virus genome contains a homologue of mammalian vascular endothelial growth factor that may enhance virulence and a vaccinia virus E3L-like gene which may inhibit the anti-viral effect of the interferons. A GM-CSF inhibitory activity has also been discovered and has been 'chased' into a 10 kb DNA segment of the orf virus genome. These studies indicate that orf virus may temporarily avoid host immunity by a combination of acute, rapid infection and replication in the epidermis and by producing virulence factors that inhibit protective proteins of the host immune and inflammatory response.
Animals↗
Altercation of generations: genetic conflicts of pregnancy.
Pregnancy is traditionally viewed as a harmonious collaboration between mother and fetus. From this perspective, viviparity poses a series of problems that maternal and fetal genes work together to solve and the many complications of pregnancy are interpreted as evidence of the malfunctioning of an evolved system or of the failure of natural selection to achieve an adaptive goal. This view fails to recognize aspects of genetic conflict that lie at the heart of gestation. At least three interrelated sources of conflict can be identified: (i) conflict between genes expressed in the mother and genes expressed in the fetus/placenta (parent-offspring conflict); (ii) conflict between maternally-derived and paternally-derived genes within the fetal genome (genomic imprinting); and (iii) conflict between maternal genes that recognize themselves in offspring and the rest of the maternal genome (gestational drive).
Animals↗
The 175 antigen expressed on myeloid and erythroid cells during differentiation is associated with serine protease activity.
Monoclonal antibody 175 recognizes a cell-surface antigen on more than 80% of nucleated ovine bone marrow cells (BMC). The distribution is unusual, as the majority of differentiated myeloid and erythroid cells express the antigen (175 antigen), whereas mast cells, basophils, and the majority of lymphocytes do not. The level of 175 antigen expression has been shown to increase as BMC differentiate during hematopoiesis. Previous attempts to identify the 175 antigen have been unsuccessful. In this study, the 175 antigen was affinity-purified and shown to contain serine protease activity. Immunoblot analysis following sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) of bone marrow cell lysates run under reducing or nonreducing conditions showed two closely adjacent protein bands (a doublet) of 28 to 30 kD molecular weight. N-linked deglycosylation showed that the 30-kD band was a glycosylated form of the 28-kD protein. Both protein bands shared the same N-terminal amino acid sequence over 20 residues, with high homology with serine proteases. Affinity-purified 175 antigen was proteolytic in substrate gels, the activity being inhibited by the 175 monoclonal antibody (Mab) and the serine protease inhibitor phenylmethylsulfonyl fluoride (PMSF), but not by metallo, thiol, or acid protease-specific inhibitors. The 175 antigen is therefore part of a growing family of cell-surface proteases associated with hematopoietic cell differentiation.
Amino Acid Sequence↗
Whitridge Williams' obstetrics.
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Ethics, Medical↗
Cohabitation and pregnancy-induced hypertension.
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Coitus↗
Cloning of a cDNA encoding ovine interleukin-3.
A cDNA encoding the ovine hematopoietic growth factor interleukin-3 (IL-3), has been cloned. A 560-bp cDNA, containing the entire protein coding region, was amplified from activated mesenteric lymph node cells. The cDNA was found to share 58% nucleotide identity with hIL-3 and 48% identity with mIL-3. The predicted ovine amino-acid sequence shares 36 and 30% identity, respectively, with the corresponding human and murine proteins.
Amino Acid Sequence↗
Generation of an ovine bone marrow-derived myelomonocyte-like cell line by retroviral-mediated transformation. Immunological characterization and the effect of cytokines and lipopolysaccharides.
A cell line (designated BMpXT1) was generated from sheep bone marrow using the Moloney murine leukemia virus-based retroviral vector pXT1. BMpXT1 cells resembled mature alveolar macrophages in being adherent and esterase positive, in expressing certain cell surface antigens, and in secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) when stimulated by ovine interferon-gamma and lipopolysaccharide (LPS) in combination. The absence of a proliferative response to ovine GM-CSF and macrophage colony-stimulating factor, the absence of other cell antigens found in mature macrophages, and low-efficiency phagocytosis suggested that the cells may be at an intermediate to late stage of myelomonocytic differentiation.
Animals↗
Refusing the ovarian time bomb.
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Animals↗
Alternatives to meiosis: the unusual genetics of red algae, microsporidia, and others.
At a reductional division, the two alleles at a heterozygous locus segregate into different daughter nuclei. Reductional divisions are therefore vulnerable to genetic elements that cause one cell to attack its sister. This danger can be circumvented by creating uncertainty about when reduction occurs. In conventional meiosis, this is achieved by a sequence of two divisions with crossing over. Either the first or the second division can be reductional for most loci. In some red algae, reduction appears to be spread over more than two divisions. The novel reduction sequence of microsporidia creates maximal uncertainty about the time of reduction in two divisions without crossing over.
Alleles↗
Genomic imprinting, human chorionic gonadotropin, and triploidy.
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Animals↗
Genetic conflicts in human pregnancy.
Pregnancy has commonly been viewed as a cooperative interaction between a mother and her fetus. The effects of natural selection on genes expressed in fetuses, however, may be opposed by the effects of natural selection on genes expressed in mothers. In this sense, a genetic conflict can be said to exist between maternal and fetal genes. Fetal genes will be selected to increase the transfer of nutrients to their fetus, and maternal genes will be selected to limit transfers in excess of some maternal optimum. Thus a process of evolutionary escalation is predicted in which fetal actions are opposed by maternal countermeasures. The phenomenon of genomic imprinting means that a similar conflict exists within fetal cells between genes that are expressed when maternally derived, and genes that are expressed when paternally derived. During implantation, fetally derived cells (trophoblast) invade the maternal endometrium and remodel the endometrial spiral arteries into low-resistance vessels that are unable to constrict. This invasion has three consequences. First, the fetus gains direct access to its mother's arterial blood. Therefore, a mother cannot reduce the nutrient content of blood reaching the placenta without reducing the nutrient supply to her own tissues. Second, the volume of blood reaching the placenta becomes largely independent of control by the local maternal vasculature. Third, the placenta is able to release hormones and other substances directly into the maternal circulation. Placental hormones, including human chorionic gonadotropin (hCG) and human placental lactogen (hPL), are predicted to manipulate maternal physiology for fetal benefit. For example, hPL is proposed to act on maternal prolactin receptors to increase maternal resistance to insulin. If unopposed, the effect of hPL would be to maintain higher blood glucose levels for longer periods after meals. This action, however, is countered by increased maternal production of insulin. Gestational diabetes develops if the mother is unable to mount an adequate response to fetal manipulation. Similarly, fetal genes are predicted to enhance the flow of maternal blood through the placenta by increasing maternal blood pressure. Preeclampsia can be interpreted as an attempt by a poorly nourished fetus to increase its supply of nutrients by increasing the resistance of its mother's peripheral circulation.
Chorionic Gonadotropin↗
The cloning and expression of the gene for ovine interleukin-3 (multi-CSF) and a comparison of the in vitro hematopoietic activity of ovine IL-3 with ovine GM-CSF and human M-CSF.
The ovine interleukin-3 (IL-3) gene has been cloned. It encodes a protein 146 amino acids (aa) in length and is situated approximately 10 kb from the gene encoding granulocyte-macrophage colony-stimulating factor (GM-CSF). A comparison of the ovine gene sequence with that of the human IL-3 gene reveals that the protein coding regions share between 49 and 59% identity, while the introns and other noncoding regions share between 63 and 78% identity. The gene promoters also share approximately 72% identity. Recombinant ovine IL-3 (rovIL-3) was expressed in Chinese hamster ovary (CHO) cells, and its biologic activity was compared to that of rovGM-CSF and recombinant human macrophage colony-stimulating factor (rhM-CSF) on ovine bone marrow cells. rovIL-3 predominantly stimulated the growth and development of mast cells and macrophages in liquid cultures and colonies of mixed cell phenotype, megakaryocytes, erythroid burst-forming units (BFU-E), and basophilic granular cells in soft agar cultures of bone marrow cells. In common with rovGM-CSF, IL-3 also stimulated eosinophil and macrophage colonies, which were increased in size and number of cells in cultures containing both cytokines. Maximum macrophage colony numbers were achieved with the combination of rovIL-3, rovGM-CSF, and rhM-CSF. rovGM-CSF stimulated neutrophil colony formation, whereas rovIL-3 did not.
Amino Acid Sequence↗
Intragenomic conflict and the evolution of eusociality.
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Animals↗
Expression and characterization of ovine major histocompatibility complex class II (OLA-DR) genes.
Previous work made use of nucleic acid probes corresponding to different subtypes of the class II regions of the human and murine major histocompatibility complex (MHC) to isolate seven different alpha and 24 different beta genes of the ovine MHC from two cosmid libraries. In an attempt to identify pairs of alpha and beta genes capable of cell surface expression, all permutations of alpha and beta genes were in turn transfected into mouse L-cells. Two pairs of alpha and beta genes co-expressed and stable ovine MHC class II L-cell lines were developed. The expressed alpha genes had previously been defined as DR-alpha homologues (DRA) by differential Southern hybridization to human subtype specific class II probes. The expressed ovine beta genes were also assigned as ovine DR-beta homologues (DRB) on the basis of their sequence having a higher degree of similarity with human DRB than any other subtype. A total of eight out of 23 anti-sheep class II specific monoclonal antibodies were typed OLA-DR specific by FACScan analysis using the L-cell lines.
Amino Acid Sequence↗