http://www.biomedcentral.com/bmcbiol/ The latest research articles published by BMC Biology 2009-07-10T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Background: Adipose tissues serve not only as a store for energy in the form of lipid, but also as endocrine tissues that regulates metabolic activities of the organism by secreting various kinds of hormones. Peroxisome proliferator activated receptor gamma (PPARgamma) is a key regulator of adipocyte differentiation that induces the expression of adipocyte-specific genes in preadipocytes and mediates their differentiation into adipocytes. Furthermore, PPARgamma has an important role to maintain the physiological function of mature adipocyte by controlling expressions of various genes properly. Therefore, any reduction in amount and activity of PPARgamma is linked to the pathogenesis of metabolic syndrome. Results: In this study, we investigated the contribution of epigenetic transcriptional regulatory mechanisms, such as DNA methylation, to the expression of the PPARgamma gene, and further evaluated the contribution of such epigenetic regulatory mechanisms to the pathogenesis of metabolic syndrome. In 3T3-L1 preadipocytes, the promoter of the PPARgamma2 gene was hypermethylated, but was progressively demethylated upon induction of differentiation, which was accompanied by an increase of mRNA expression. Moreover, treatment of cells with 5'-aza-cytideine, an inhibitor of DNA methylation, increased expression of the PPARgamma gene in a dose-dependent manner. Methylation in vitro of a PPARgamma promoter-driven reporter construct also repressed the transcription of a downstream reporter gene. These results suggest that the expression of the PPARgamma gene is inhibited by methylation of its promoter. We next compared the methylation status of the PPARgamma promoters in adipocytes from wild-type (WT) mice with those from two diabetic mouse models: +Leprdb/+Leprdb and diet-induced obesity mice. Interestingly, we found increased methylation of the PPARgamma promoter in visceral adipose tissues (VAT) of the mouse models of diabetes, compared to that observed in wild-type mice. We observed a concomitant decrease in the level of PPARgamma mRNA in the diabetic mice compared to the WT mice. Conclusions: We conclude that the expression of PPARgamma gene is regulated by DNA methylation of its promoter region and propose that reduced expression of PPARgamma owing to DNA methylation in adipocytes of the VAT may contribute to the pathogenesis of metabolic syndrome. http://www.biomedcentral.com/1741-7007/7/38 Katsunori Fujiki Fumi Kano Kunio Shiota Masayuki Murata BMC Biology 2009, 7:38 2009-07-10T00:00:00Z doi:10.1186/1741-7007-7-38 BMC Biology 1741-7007 7 38 2009-07-10T00:00:00Z PDF Background: Executive functions, learning and attention are imperative facets of cognitive performance, affected in many neuropsychiatric disorders. Recently, we have shown that recombinant human erythropoietin improves cognitive functions in patients with chronic schizophrenia, and that it leads in healthy mice to enhanced hippocampal long-term potentiation, an electrophysiological correlate of learning and memory. To create an experimental basis for further mechanistic insight into erythropoietin-modulated cognitive processes, we employed the Five Choice Serial Reaction Time Task. This procedure allows the study of the effects of erythropoietin on discrete processes of learning and attention in a sequential fashion. Results: Male mice were treated for 3 weeks with erythropoietin (5,000 IU/kg) versus placebo intraperitoneally every other day, beginning at postnatal day 28. After termination of treatment, mice were started on the Five Choice Serial Reaction Time Task, with daily training and testing extending to about 3 months.Overall, a significantly higher proportion of erythropoietin-treated mice finished the task, that is, reached the criteria of adequately reacting to a 1.0 sec flash light out of five arbitrarily appearing choices. During acquisition of this capability, that is, over almost all sequential training phases, learning readouts (magazine training, operant and discriminant learning, stability of performance) were superior in erythropoietin-treated versus control mice. Conclusions: Early erythropoietin treatment leads to lasting improvement of cognitive performance in healthy mice. This finding should be exploited in novel treatment strategies for brain diseases. http://www.biomedcentral.com/1741-7007/7/37 Ahmed El-Kordi Konstantin Radyushkin Hannelore Ehrenreich BMC Biology 2009, 7:37 2009-07-08T00:00:00Z doi:10.1186/1741-7007-7-37 BMC Biology 1741-7007 7 37 2009-07-08T00:00:00Z PDF As a result of the integration of molecular and morphological approaches for the reconstruction of phylogenies, and of the intertwining of developmental and evolutionary biology, further prospects are open for a fruitful interaction between these two fields in what we may call a phylo-evo-devo approach.Wiegmann et al.'s molecular phylogeny of the holometabolous insect orders, recently published in BMC Biology, offers a good opportunity to revisit the inverted positions of wings and halteres in the Diptera and the Strepsiptera in terms of a putative homeotic mutation in the Hox gene Ultrabithorax. The main finding of this paper is that Strepsiptera are closely related to the Coleoptera rather than Diptera, as recently claimed. Through this exemplary case, the paper demonstrates the value of the reciprocal illumination we can expect from the integration of a good phylogeny and a sound knowledge of the evolvability of developmental mechanisms. http://www.biomedcentral.com/1741-7007/7/36 Alessandro Minelli BMC Biology 2009, 7:36 2009-06-26T00:00:00Z doi:10.1186/1741-7007-7-36 BMC Biology 1741-7007 7 36 2009-06-26T00:00:00Z XML Background: The p53 tumor suppressor and its related protein, p73, share a homologous DNA binding domain, and mouse genetics studies have suggested that they have overlapping as well as distinct biological functions. Both p53 and p73 are activated by genotoxic stress to regulate an array of cellular responses. Previous studies have suggested that p53 and p73 independently activate the cellular apoptotic program in response to cytotoxic drugs. The goal of this study was to compare the promoter-binding activity of p53 and p73 at steady state and after genotoxic stress induced by hydroxyurea. Results: We employed chromatin immunoprecipitation, the NimbleGen promoter arrays and a model-based algorithm for promoter arrays to identify promoter sequences enriched in anti-p53 or anti-p73 immunoprecipitates, either before or after treatment with hydroxyurea, which increased the expression of both p53 and p73 in the human colon cancer cell line HCT116-3(6). We calculated a model-based algorithm for promoter array score for each promoter and found a significant correlation between the promoter occupancy profiles of p53 and p73. We also found that after hydroxyurea treatment, the p53-bound promoters were still bound by p73, but p73 became associated with additional promoters that that did not bind p53. In particular, we showed that hydroxyurea induces the binding of p73 but not p53 to the promoter of MLH3, which encodes a mismatch repair protein, and causes an up-regulation of the MLH3 mRNA. Conclusion: These results suggest that hydroxyurea exerts differential effects on the promoter-binding functions of p53 and p73 and illustrate the power of model-based algorithm for promoter array in the analyses of promoter occupancy profiles of highly homologous transcription factors. http://www.biomedcentral.com/1741-7007/7/35 Vera Huang Xin Lu Yong Jiang Jean Wang BMC Biology 2009, 7:35 2009-06-26T00:00:00Z doi:10.1186/1741-7007-7-35 BMC Biology 1741-7007 7 35 2009-06-26T00:00:00Z PDF Background: Evolutionary relationships among the 11 extant orders of insects that undergo complete metamorphosis, called Holometabola, remain either unresolved or contentious, but are extremely important as a context for accurate comparative biology of insect model organisms. The most phylogenetically enigmatic holometabolan insects are Strepsiptera or twisted wing parasites, whose evolutionary relationship to any other insect order is unconfirmed. They have been controversially proposed as the closest relatives of the flies, based on rDNA, and a possible homeotic transformation in the common ancestor of both groups that would make the reduced forewings of Strepsiptera homologous to the reduced hindwings of Diptera. Here we present evidence from nucleotide sequences of six single-copy nuclear protein coding genes used to reconstruct phylogenetic relationships and estimate evolutionary divergence times for all holometabolan orders. Results: Our results strongly support Hymenoptera as the earliest branching holometabolan lineage, the monophyly of the extant orders, including the fleas, and traditionally recognized groupings of Neuropteroidea and Mecopterida. Most significantly, we find strong support for a close relationship between Coleoptera (beetles) and Strepsiptera, a previously proposed, but analytically controversial relationship. Exploratory analyses reveal that this relationship cannot be explained by long-branch attraction or other systematic biases. Bayesian divergence times analysis, with reference to specific fossil constraints, places the origin of Holometabola in the Carboniferous (355 Ma), a date significantly older than previous paleontological and morphological phylogenetic reconstructions. The origin and diversification of most extant insect orders began in the Triassic, but flourished in the Jurassic, with multiple adaptive radiations producing the astounding diversity of insect species for which these groups are so well known. Conclusion: These findings provide the most complete evolutionary framework for future comparative studies on holometabolous model organisms and contribute strong evidence for the resolution of the 'Strepsiptera problem', a long-standing and hotly debated issue in insect phylogenetics. http://www.biomedcentral.com/1741-7007/7/34 Brian Wiegmann Michelle Trautwein Jung-Wook Kim Brian Cassel Matthew Bertone Shaun Winterton David Yeates BMC Biology 2009, 7:34 2009-06-24T00:00:00Z doi:10.1186/1741-7007-7-34 BMC Biology 1741-7007 7 34 2009-06-24T00:00:00Z XML Background: To survive and reproduce, animals must be able to modify their motor behavior in response to changes in the environment. We studied a complex behavior of Caenorhabditis elegans, male mating behavior, which provided a model for understanding motor behaviors at the genetic, molecular as well as circuit level. C. elegans male mating behavior consists of a series of six sub-steps: response to contact, backing, turning, vulva location, spicule insertion, and sperm transfer. The male tail contains most of the sensory structures required for mating, in addition to the copulatory structures, and thus to carry out the steps of mating behavior, the male must keep his tail in contact with the hermaphrodite. However, because the hermaphrodite does not play an active role in mating and continues moving, the male must modify his tail posture to maintain contact. We provide a better understanding of the molecular and neuro-muscular pathways that regulate male tail posture during mating. Results: Genetic and laser ablation analysis, in conjunction with behavioral assays were used to determine neurotransmitters, receptors, neurons and muscles required for the regulation of male tail posture. We showed that proper male tail posture is maintained by the coordinated activity of opposing muscle groups that curl the tail ventrally and dorsally. Specifically, acetylcholine regulates both ventral and dorsal curling of the male tail, partially through anthelmintic levamisole-sensitive, nicotinic receptor subunits. Male-specific muscles are required for acetylcholine-driven ventral curling of the male tail but dorsal curling requires the dorsal body wall muscles shared by males and hermaphrodites. Gamma-aminobutyric acid activity is required for both dorsal and ventral acetylcholine-induced curling of the male tail and an inhibitory gamma-aminobutyric acid receptor, UNC-49, prevents over-curling of the male tail during mating, suggesting that cross-inhibition of muscle groups helps maintain proper tail posture. Conclusion: Our results demonstrated that coordination of opposing sex-specific and core muscle groups, through the activity of multiple neurotransmitters, is required for regulation of male tail posture during mating. We have provided a simple model for regulation of male tail posture that provides a foundation for studies of how genes, molecular pathways, and neural circuits contribute to sensory regulation of this motor behavior. http://www.biomedcentral.com/1741-7007/7/33 Allyson Whittaker Paul Sternberg BMC Biology 2009, 7:33 2009-06-22T00:00:00Z doi:10.1186/1741-7007-7-33 BMC Biology 1741-7007 7 33 2009-06-22T00:00:00Z PDF Background: Dispersal plays a key role in shaping biological and ecological processes such as the distribution of spatially-structured populations or the pace and scale of invasion. Here we have studied the relationship between long-distance dispersal behaviour of a pest-controlling money spider, Erigone atra, and the distribution of maternally acquired endosymbionts within the wider meta-population. This spider persists in heterogeneous environments because of its ability to recolonise areas through active long-distance airborne dispersal using silk as a sail, in a process termed 'ballooning'. Results: We show that there is spatial heterogeneity in the prevalence of two maternally acquired endosymbiont infections within the wider E. atra meta-population and we demonstrate through several independent approaches a link between the presence of one of these endosymbionts, Rickettsia, and the tendency for long-distance movement. Conclusion: This novel finding that particular endosymbionts can influence host dispersal is of broad importance given the extremely widespread occurrence of similar bacteria within arthropod communities. A bacterial phenotype that limits dispersal has the potential not only to reduce gene flow and thus contribute to degrees of reproductive isolation within species, but also to influence species distribution and thus overall community composition. http://www.biomedcentral.com/1741-7007/7/32 Sara Goodacre Oliver Martin Dries Bonte Linda Hutchings Chris Woolley Kamal Ibrahim C.F. George Thomas Godfrey Hewitt BMC Biology 2009, 7:32 2009-06-19T00:00:00Z doi:10.1186/1741-7007-7-32 BMC Biology 1741-7007 7 32 2009-06-19T00:00:00Z XML Background: Delta opioid peptide [D-ala2,D-leU5]enkephalin (DADLE) induces hibernation in summer ground squirrels, and enhances preservation and survival of isolated or transplanted lungs and hearts. In the present study, we investigated the protective effect of DADLE in the central nervous system. Results: Adult Sprague-Dawley rats were pretreated with DADLE (4 mg/kg every 2 h × 4 injections, i.p.) or saline prior to unilateral occlusion of the middle cerebral artery (MCA). Daily behavioral tests revealed that ischemic animals treated with DADLE did not show any significant behavioral dysfunctions compared with saline-treated ischemic animals. Opioid antagonists only transiently inhibited the protective effect of DADLE, indicating the participation of non-opioid mechanisms in DADLE neuroprotection. Histological examination using triphenyltetrazolium chloride (TTC) revealed that brains from ischemic animals treated with DADLE, either alone or with adjuvant opioid blockers, exhibited almost completely intact striata. In contrast, brains from ischemic animals that received saline showed significant infarction in the lateral striatum. Analyses of apoptotic cell death revealed a significant increase in the p-53 mRNA expression in the striatum of ischemic animals that received saline, while those that received DADLE exhibited near normal striatal p-53 expression. This protective effect was accompanied by significant increments in protein levels of glial cell line-derived neurotrophic factor in the striatum of DADLE-treated ischemic animals. Conclusion: These results indicate that DADLE protected against necrotic and apoptotic cell death processes associated with ischemia-reperfusion injury. The present study demonstrates that delta opioids are crucially involved in stroke, suggesting that the opioid system is important in the study of brain injury and protection. http://www.biomedcentral.com/1741-7007/7/31 Cesar Borlongan Teruo Hayashi Peter Oeltgen Tsung-Ping Su Yun Wang BMC Biology 2009, 7:31 2009-06-17T00:00:00Z doi:10.1186/1741-7007-7-31 BMC Biology 1741-7007 7 31 2009-06-17T00:00:00Z XML Background: Synaptic plasticity associated with an important wave of gene transcription and protein synthesis underlies long-term memory processes. Calcium (Ca2+) plays an important role in a variety of neuronal functions and indirect evidence suggests that it may be involved in synaptic plasticity and in the regulation of gene expression correlated to long-term memory formation. The aim of this study was to determine whether Ca2+ is necessary and sufficient for inducing long-term memory formation. A suitable model to address this question is the Pavlovian appetitive conditioning of the proboscis extension reflex in the honeybee Apis mellifera, in which animals learn to associate an odor with a sucrose reward. Results: By modulating the intracellular Ca2+ concentration ([Ca2+]i) in the brain, we show that: (i) blocking [Ca2+]i increase during multiple-trial conditioning selectively impairs long-term memory performance; (ii) conversely, increasing [Ca2+]i during single-trial conditioning triggers long-term memory formation; and finally, (iii) as was the case for long-term memory produced by multiple-trial conditioning, enhancement of long-term memory performance induced by a [Ca2+]i increase depends on de novo protein synthesis. Conclusion: Altogether our data suggest that during olfactory conditioning Ca2+ is both a necessary and a sufficient signal for the formation of protein-dependent long-term memory. Ca2+ therefore appears to act as a switch between short- and long-term storage of learned information. http://www.biomedcentral.com/1741-7007/7/30 Emmanuel Perisse Valerie Raymond-Delpech Isabelle Neant Yukihisa Matsumoto Catherine Leclerc Marc Moreau Jean-Christophe Sandoz BMC Biology 2009, 7:30 2009-06-16T00:00:00Z doi:10.1186/1741-7007-7-30 BMC Biology 1741-7007 7 30 2009-06-16T00:00:00Z PDF Background: Aggressive behavior in animals is important for survival and reproduction. Identifying the underlying genes and environmental contexts that affect aggressive behavior is important for understanding the evolutionary forces that maintain variation for aggressive behavior in natural populations, and to develop therapeutic interventions to modulate extreme levels of aggressive behavior in humans. While the role of neurotransmitters and a few other molecules in mediating and modulating levels of aggression is well established, it is likely that many additional genetic pathways remain undiscovered. Drosophila melanogaster has recently been established as an excellent model organism for studying the genetic basis of aggressive behavior. Here, we present the results of a screen of 170 Drosophila P-element insertional mutations for quantitative differences in aggressive behavior from their co-isogenic control line. Results: We identified 59 mutations in 57 genes that affect aggressive behavior, none of which had been previously implicated to affect aggression. Thirty-two of these mutants exhibited increased aggression, while 27 lines were less aggressive than the control. Many of the genes affect the development and function of the nervous system, and are thus plausibly relevant to the execution of complex behaviors. Others affect basic cellular and metabolic processes, or are mutations in computationally predicted genes for which aggressive behavior is the first biological annotation. Most of the mutations had pleiotropic effects on other complex traits. We characterized nine of these mutations in greater detail by assessing transcript levels throughout development, morphological changes in the mushroom bodies, and restoration of control levels of aggression in revertant alleles. All of the P-element insertions affected the tagged genes, and had pleiotropic effects on brain morphology. Conclusion: This study reveals that many more genes than previously suspected affect aggressive behavior, and that these genes have widespread pleiotropic effects. Given the conservation of aggressive behavior among different animal species, these are novel candidate genes for future study in other animals, including humans. http://www.biomedcentral.com/1741-7007/7/29 Alexis Edwards Liesbeth Zwarts Akihiko Yamamoto Patrick Callaerts Trudy Mackay BMC Biology 2009, 7:29 2009-06-11T00:00:00Z doi:10.1186/1741-7007-7-29 BMC Biology 1741-7007 7 29 2009-06-11T00:00:00Z XML