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  • Modulation of social interactions by immune stimulation in honey bee workers, Apis mellifera
    Background: Immune response pathways have been relatively well-conserved across animal species, with similar systems in both mammals and invertebrates. Interestingly, honey bees have substantially reduced numbers of genes associated with immune function compared to solitary insect species. However social species such as honey bees provide an excellent environment for pathogen or parasite transmission, with controlled environmental conditions in the hive, high population densities, and frequent interactions. This suggests that honey bees may have developed complementary mechanisms - such as behavioural modifications - to deal with disease. Results: Here, we demonstrate that activation of the immune system in honey bees (using bacterial lipopolysaccharides, LPS, as a non-replicative pathogen) alters the social responses of healthy nestmates toward the treated individuals. Furthermore, treated individuals expressed significant differences in overall cuticular hydrocarbon profiles compared to controls. Finally, coating healthy individuals with extracts containing cuticular hydrocarbons of immunostimulated individuals significantly increased the agonistic responses of nestmates. Conclusion: Since cuticular hydrocarbons play a critical role in nestmate recognition and other social interactions in a wide variety of insect species, modulation of such chemical profiles by the activation of the immune system could play a crucial role in the social regulation of pathogen dissemination within the colony.

  • A comprehensive functional analysis of tissue specificity of human gene expression
    Background: In recent years, the maturation of microarray technology has allowed the genome-wide analysis of gene expression patterns to identify tissue-specific and ubiquitously-expressed ("housekeeping") genes. We have performed a functional and topological analysis of housekeeping and tissue-specific networks to identify universally-necessary biological processes, and those unique to or characteristic of particular tissues. Results: We measured whole genome expression in 31 human tissues, identifying 2,374 housekeeping (HK) genes expressed in all tissues, and genes uniquely expressed in each tissue. Comprehensive functional analysis showed that the HK set is substantially larger than previously thought, and is enriched with vital processes such as oxidative phosphorylation, ubiquitin-dependent proteolysis, translation, and energy metabolism. Network topology of the HK network was characterized by higher connectivity and shorter paths between the proteins than the global network. Ontology enrichment scoring and network topology of tissue-specific genes were consistent with each tissue's function and expression patterns clustered together in accordance with tissue origin. Tissue-specific genes were twice as likely as HK genes to be drug targets, allowing the identification of tissue "signature networks" that will facilitate the discovery of new therapeutic targets and biomarkers of tissue-targeted diseases. Conclusions: A comprehensive functional analysis of housekeeping and tissue specific genes showed that the biological function of housekeeping and tissue-specific genes were consistent with tissue origin. Network analysis revealed that tissue-specific networks have distinct network properties related to each tissue's function. Tissue "signature networks" promise to be a rich source of targets and biomarkers for disease treatment and diagnosis.

  • Lack of functional alpha-lactalbumin prevents involution in Cape fur seals and identifies the protein is an apoptotic milk factor in mammary gland involution
    Background: The mammary gland undergoes a sophisticated program of developmental changes during pregnancy and lactation, however little is known about processes involving initiation of apoptosis at involution following weaning. We used fur seals as models to study the molecular process of involution as these animals display a unique mammary gland phenotype. Fur seals have long lactation periods whereby mothers cycle between secreting copious quantities of milk for 2-3 days suckling pups on land, with trips to sea alone to forage for up to 23 days during which time mammary glands remain active without initiating apoptosis or involution. Results: We show the molecular basis by which alpha-lactalbumin (LALBA), a secreted milk protein, is absent in Cape fur seals and demonstrate an apoptotic function for LALBA when exposed to mammary cells. Conclusion: We propose that apoptosis does not occur in fur seal mammary glands due to lack of LALBA in fur seal milk, allowing evasion of involution during a foraging trip. Our work identifies LALBA as a milk factor which feeds back on the mammary gland to regulate involution.

  • Knee-clicks and visual traits indicate fighting ability in eland antelopes: multiple messages and back-up signals
    Background: Given the costs of signalling, why do males often advertise their fighting ability to rivals using several signals rather than just one? Multiple signalling theories have developed largely in studies of sexual signals, and less is known about their applicability to intra-sexual communication. We here investigate the evolutionary basis for the intricate agonistic signalling system in eland antelopes, paying particular attention to the evolutionary phenomenon of loud knee-clicking. Results: A principal components analysis separated seven male traits into three groups. The dominant frequency of the knee-clicking sound honestly indicated body size, a main determinant of fighting ability. In contrast, the dewlap size increased with estimated age rather than body size, suggesting that, by magnifying the silhouette of older bulls disproportionately, the dewlap acts as an indicator of age-related traits such as fighting experience. Facemask darkness, frontal hairbrush size and body greyness aligned with a third underlying variable, presumed to be androgen-related aggression. A longitudinal study provided independent support of these findings. Conclusion: The results show that the multiple agonistic signals in eland reflect three separate components of fighting ability: (1) body size, (2) age and (3) presumably androgen-related aggression, which is reflected in three backup signals. The study highlights how complex agonistic signalling systems can evolve through the simultaneous action of several selective forces, each of which favours multiple signals. Specifically, loud knee-clicking is discovered to be an honest signal of body size, providing an exceptional example of the potential for non-vocal acoustic communication in mammals.

  • Positive correlation between genetic diversity and fitness in a large, well-connected metapopulation
    Background: Theory predicts that lower dispersal, and associated gene flow, leads to decreased genetic diversity in small isolated populations, which generates adverse consequences on fitness, and subsequently on demography. Here we report for the first time this effect in a well-connected natural butterfly metapopulation with high population densities at the edge of its distribution range. Results: We demonstrate that: (1) lower genetic diversity was coupled to a sharp decrease in adult lifetime expectancy, a key component of individual fitness; (2) genetic diversity was positively correlated to number of dispersing individuals (indicative of landscape functional connectivity) and adult population size; (3) parameters inferred from capture-recapture procedures (population size and dispersal events between patches) correlated much better with genetic diversity than estimates usually used as surrogates for population size (patch area and descriptors of habitat quality) and dispersal (structural connectivity index). Conclusion: Our results suggest that dispersal is a very important factor maintaining genetic diversity. Even at a very local spatial scale in a metapopulation consisting of large high-density populations interconnected by considerable dispersal rates, genetic diversity can be decreased and directly affect the fitness of individuals. From a biodiversity conservation perspective, this study clearly shows the benefits of both in-depth demographic and genetic analyses. Accordingly, to ensure the long-term survival of populations, conservation actions should not be blindly based on patch area and structural isolation. This result may be especially pertinent for species at their range margins, particularly in this era of rapid environmental change.

  • Y chromosome evidence of earliest modern human settlement in East Asia and multiple origins of Tibetan and Japanese populations
    Background: The phylogeography of the Y chromosome in Asia previously suggested that modern humans of African origin initially settled in mainland southern East Asia, and about 25,000-30,000 years ago, migrated northward, spreading throughout East Asia. However, the fragmented distribution of one East Asian specific Y chromosome lineage (D-M174), which is found at high frequencies only in Tibet, Japan and the Andaman Islands, is inconsistent with this scenario. Results: In this study, we collected more than 5,000 male samples from 73 East Asian populations and reconstructed the phylogeography of the D-M174 lineage. Our results suggest that D-M174 represents an extremely ancient lineage of modern humans in East Asia, and a deep divergence was observed between northern and southern populations. Conclusions: We proposed that D-M174 has a southern origin and its northward expansion occurred about 60,000 years ago, predating the northward migration of other major East Asian lineages. The Neolithic expansion of Han culture and the last glacial maximum are likely the key factors leading to the current relic distribution of D-M174 in East Asia. The Tibetan and Japanese populations are the admixture of two ancient populations represented by two major East Asian specific Y chromosome lineages, the O and D haplogroups.

  • The molecular basis of defective lens development in the Iberian Mole
    Background: Fossorial mammals face natural selection pressures that differ from those acting on surface dwelling animals, and these may lead to reduced visual system development. We have studied eye development in a species of true mole, the Iberian mole Talpa occidentalis, and present the molecular basis of abnormal lens development. This is the first embryological developmental study of the eyes of any fossorial mammal at the molecular level. Results: Lens fibre differentiation is not completed in the Iberian mole. Although eye development starts normally (similar to other model species), defects are seen after closure of the lens vesicle. PAX6 is not downregulated in developing lens fibre nuclei, as it is in other species, and there is ectopic expression of FOXE3, a putative downstream effector of PAX6, in some but not all lens fibres. FOXE3-positive lens fibres continue to proliferate within the posterior compartment of the embryonic lens, but unlike in the mouse, no proliferation was detected anywhere in the postnatal mole lens. The undifferentiated status of the anterior epithelial cells was compromised, and most of them undergo apoptosis. Furthermore, beta-crystallin and PROX1 expression patterns are abnormal and our data suggest that beta-crystallin genes are not directly regulated by PAX6, c-MAF and PROX1 in Talpa occidentalis, as they are in other model vertebrates. Conclusions: In other model vertebrates, genetic pathways controlling lens development robustly compartmentalise the lens into a simple, undifferentiated, proliferative anterior epithelium, and quiescent, anuclear, terminally differentiated posterior lens fibres. These pathways are not as robust in the mole, and lead to loss of the anterior epithelial phenotype and only partial differentiation of the lens fibres, which continue to express 'epithelial' genes. Paradigms of genetic regulatory networks developed in other vertebrates appear not to hold true for the Iberian mole.

  • Identification of the Weevil immune genes and their expression in the bacteriome tissue
    Background: Persistent infections with mutualistic intracellular bacteria (endosymbionts) are well represented in insects and are considered to be a driving force in evolution. However, while pathogenic relationships have been well studied over the last decades very little is known about the recognition of the endosymbionts by the host immune system and the mechanism that limits their infection to the bacteria-bearing host tissue (the bacteriome). Results: To study bacteriome immune specificity, we first identified immune-relevant genes of the weevil Sitophilus zeamais by using suppressive subtractive hybridization (SSH) and then analyzed their full-length coding sequences obtained by RACE-PCR experiments. We then measured immune gene expression in the bacteriome, and in the aposymbiotic larvae following S. zeamais primary endosymbiont (SZPE) injection into the hemolymph, in order to consider the questions of bacteriome immune specificity and the insect humoral response to symbionts. We show that larval challenge with the endosymbiont results in a significant induction of antibacterial peptide genes, providing evidence that, outside the bacteriome, SZPE are recognized as microbial intruders by the host. In the bacteriome, gene expression analysis shows the overexpression of one antibacterial peptide from the coleoptericin family and, intriguingly, homologs to genes described as immune modulators (that is, PGRP-LB, Tollip) were also shown to be highly expressed in the bacteriome. Conclusion: The current data provide the first description of immune gene expression in the insect bacteriome. Compared with the insect humoral response to SZPE, the bacteriome expresses few genes among those investigated in this work. This local immune gene expression may help to maintain the endosymbiont in the bacteriome and prevent its invasion into insect tissues. Further investigations of the coleoptericin, the PGRP and the Tollip genes should elucidate the role of the host immune system in the maintenance and regulation of endosymbiosis.

  • The Caenorhabditis chemoreceptor gene families
    Background: Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Results: Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Conclusion: Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.

  • Resilin and chitinous cuticle form a composite structure for energy storage in jumping by froghopper insects
    Background: Many insects jump by storing and releasing energy in elastic structures within their bodies. This allows them to release large amounts of energy in a very short time to jump at very high speeds. The fastest of the insect jumpers, the froghopper, uses a catapult-like elastic mechanism to achieve their jumping prowess in which energy, generated by the slow contraction of muscles, is released suddenly to power rapid and synchronous movements of the hind legs. How is this energy stored? Results: The hind coxae of the froghopper are linked to the hinges of the ipsilateral hind wings by pleural arches, complex bow-shaped internal skeletal structures. They are built of chitinous cuticle and the rubber-like protein, resilin, which fluoresces bright blue when illuminated with ultra-violet light. The ventral and posterior end of this fluorescent region forms the thoracic part of the pivot with a hind coxa. No other structures in the thorax or hind legs show this blue fluorescence and it is not found in larvae which do not jump. Stimulating one trochanteral depressor muscle in a pattern that simulates its normal action, results in a distortion and forward movement of the posterior part of a pleural arch by 40 μm, but in natural jumping, the movement is at least 100 μm. Conclusion: Calculations showed that the resilin itself could only store 1% to 2% of the energy required for jumping. The stiffer cuticular parts of the pleural arches could, however, easily meet all the energy storage needs. The composite structure therefore, combines the stiffness of the chitinous cuticle with the elasticity of resilin. Muscle contractions bend the chitinous cuticle with little deformation and therefore, store the energy needed for jumping, while the resilin rapidly returns its stored energy and thus restores the body to its original shape after a jump and allows repeated jumping.


Robyne Wilkerson
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