The evolution of haplodiploidy by male‐killing endosymbionts: importance of population structure and endosymbiont mutualisms

Haplodiploid inheritance systems, characterized by male transmission of only their maternally inherited genomic elements, have evolved more than 20 times within the animal kingdom. A number of theoretical studies have argued that infection with certain male‐killing endosymbionts can potentially lead to the evolution of haplodiploidy. By explicitly investigating the coevolutionary dynamics between host and endosymbiont, we show that the assumptions of current models cannot explain the evolution of haplodiploidy very well, as the endosymbiont will often go extinct in the long term. Here, we provide two additional mechanisms that can explain the stable evolution of haplodiploidy by male‐killing endosymbionts. First of all, a spatially structured population can facilitate the long‐term persistence of haplodiploidy, but this applies only when levels of inbreeding are very high. By contrast, endosymbionts that are mutualistic with their hosts provide a much more general and promising route to the stable evolution of haplodiploidy. This model is the first to provide a formal explanation of the supposed association between the evolution of haplodiploidy and the highly inbred lifestyles of some ancestors, while it also provides a hypothesis for the evolution of haplodiploidy in more outbred ancestors.     

Classifying Integrated Signature Molecules in Macrophages of Rheumatoid Arthritis,Osteoarthritis, and Periodontal Disease: An Omics-Based Study

Rheumatoid arthritis (RA), osteoarthritis (OA), and periodontal disease (PD) are chronic inflammatory diseases that are globally prevalent, and pose a public health concern. The search for a potential mechanism linking PD to RA and OA continues, as it could play a significant role in disease prevention and treatment. Recent studies have linked RA, OA, and PD to Porphyromonas gingivalis (PG), a periodontal bacterium, through a similar dysregulation in an inflammatory mechanism. This study aimed to identify potential gene signatures that could assist in early diagnosis as well as gain insight into the molecular mechanisms of these diseases. The expression data sets with the series IDs {"type":"entrez-geo","attrs":{"text":"GSE97779","term_id":"97779"}}GSE97779, {"type":"entrez-geo","attrs":{"text":"GSE123492","term_id":"123492"}}GSE123492, and {"type":"entrez-geo","attrs":{"text":"GSE24897","term_id":"24897"}}GSE24897 for macrophages of RA, OA synovium, and PG stimulated macrophages (PG-SM), respectively, were retrieved and screened for differentially expressed genes (DEGs). The 72 common DEGs among RA, OA, and PG-SM were further subjected to gene–gene correlation analysis. A GeneMANIA interaction network of the 47 highly correlated DEGs comprises 53 nodes and 271 edges. Network centrality analysis identified 15 hub genes, 6 of which are DEGs (API5, ATE1, CCNG1, EHD1, RIN2, and STK39). Additionally, two significantly up-regulated non-hub genes (IER3 and RGS16) showed interactions with hub genes. Functional enrichment analysis of the genes showed that “apoptotic regulation” and “inflammasomes” were among the major pathways. These eight genes can serve as important signatures/targets, and provide new insights into the molecular mechanism of PG-induced RA, OA, and PD.     

Lymphadenitis,trans-epidermal elimination and unusualhistopathology in human rhinosporidiosis

From a study of rhinosporidial tissues of 64 human cases of ocular, urethral and nasopharyngeal disease, unusual histopathological features of 27 cases are described. Histopathological evidence of lymphadenitis in rhinosporidiosis is presented for the first time. The phenomenon of `trans-epidermal elimination' of sporangia of the causative pathogen Rhinosporidium seeberi is illustrated and it is argued that this phenomenon is rather the pathogen's mechanism for endospore-dispersal than a non-specific defence reaction of the host as has previously been suggested. Other unusual appearances described include variations in the intensity and composition of the host-cell infiltrate in tissues from different patients and in different portions of the same tissue, pitfalls in histopathological diagnosis, and unusual appearances of the pathogen. Histopathological clues to the pathogenesis of rhinosporidiosis and mechanisms of anti-rhinosporidial immunity in the host are discussed, illustrating the probable occurrence of immunesuppressive reactions to account for the variations in the density and composition of the host-cell infiltrate and the state of the rhinosporidial sporangia – intact or degenerate –, relating these variations to the chronicity, recurrences and systemic dissemination of rhinosporidiosis. This revised version was published online in June 2006 with corrections to the Cover Date.     

Computer simulation of the delivery of etanidazole to brain tumor from PLGA wafers: comparison between linear and double burst release systems

This paper presents the computer simulation results on the delivery of Etanidazole (radiosensitizer) to the brain tumor and examines several factors affecting the delivery. The simulation consists of a 3D model of tumor with poly(lactide-co-glycolide) (PLGA) wafers with 1% Etanidazole loading implanted in the resected cavity. A zero-order release device will produce a concentration profile in the tumor which increases with time until the drug in the carrier is depleted. This causes toxicity complications during the later stages of drug treatment. However, for wafers of similar loading, such release results in a higher drug penetration depth and therapeutic index as compared to the double drug burst profile. The numerical accuracy of the model was verified by the similar results obtained in the two-dimensional and three-dimensional models.     

Genome downsizing in polyploid plants

All else being equal, polyploids are expected to have larger C-values (amount of DNA in the unreplicated gametic nucleus) than their diploid progenitors, increasing in direct proportion with ploidy. This expectation is observed in some polyploid series, especially those newly formed, but there are examples suggesting that C-values in particular polyploids are less than expected. The availability of the Angiosperm DNA C-values database ( http://www.rbgkew.org.uk/cval/homepage.html ) has allowed this question to be addressed across a broad range of angiosperms and has revealed striking results deviating from expectation: (i) mean 1C DNA amount did not increase in direct proportion with ploidy, and (ii) mean DNA amount per basic genome (calculated by dividing the 2C value by ploidy) tended to decrease with increasing ploidy. These results suggest that loss of DNA following polyploid formation, or genome downsizing, may be a widespread phenomenon of considerable biological significance. Recent advances in our understanding of the molecular events that take place following polyploid formation together with new data on how DNA amounts can both increase and decrease provide some insights into how genome downsizing may take place. The nature of the evolutionary forces that may be driving DNA loss are also discussed.  © 2004 The Linnean Society of London, Biological Journal of the Linnean Society , 2004, 82 , 651–663.     

Improved specificity of reagentless amperometric PQQ-sGDH glucose biosensors by using indirectly heated electrodes

Indirectly heated electrodes operating in a non-isothermal mode have been used as transducers for reagentless glucose biosensors. Pyrroloquinoline quinone-dependent soluble glucose dehydrogenase (PQQ-sGDH) was entrapped on the electrode surface within a redox hydrogel layer. Localized polymer film precipitation was invoked by electrochemically modulating the pH-value in the diffusion zone in front of the electrode. The resulting decrease in solubility of an anodic electrodeposition paint (EDP) functionalized with Osmium complexes leads to precipitation of the redox hydrogel concomitantly entrapping the enzyme. The resulting sensor architecture enables a fast electron transfer between enzyme and electrode surface. The glucose sensor was operated at pre-defined temperatures using a multiple current-pulse mode allowing reproducible indirect heating of the sensor. The sensor characteristics such as the apparent Michaelis constants K(M)(app) and maximum currents I(max)(app) were determined at different temperatures for the main substrate glucose as well as a potential interfering co-substrate maltose. The limit of detection increased with higher temperatures for both substrates (0.020 mM for glucose, and 0.023 mM for maltose at 48 degrees C). The substrate specificity of PQQ-sGDH is highly temperature dependent. Therefore, a mathematical model based on a multiple linear regression approach could be applied to discriminate between the current response for glucose and maltose. This allowed accurate determination of glucose in a concentration range of 0-0.1mM in the presence of unknown maltose concentrations ranging from 0 to 0.04 mM.     

Apoptosis signal-regulating kinase 1 is mediated in TNF-α-induced CCL2 expression in human synovial fibroblasts

Tumor necrosis factor‐α (TNF‐α), a pro‐inflammatory cytokine with a critical role in osteoarthritis (OA), was primarily produced by monocytes/macrophages and plays a crucial role in the inflammatory response. Here, we investigated the intracellular signaling pathways involved in TNF‐α‐induced monocyte chemoattractant protein 1 (MCP‐1)/CCL2 expression in human synovial fibroblast cells. Stimulation of synovial fibroblasts (OASF) with TNF‐α induced concentration‐ and time‐dependent increases in CCL2 expression. TNF‐α‐mediated CCL2 production was attenuated by TNFR1 monoclonal antibody (Ab). Pretreatment with an apoptosis signal‐regulating kinase 1 (ASK1) inhibitor (thioredoxin), JNK inhibitor (SP600125), p38 inhibitor (SB203580), or AP‐1 inhibitor (curcumin or tanshinone IIA) also blocked the potentiating action of TNF‐α. Stimulation of cells with TNF‐α enhanced ASK1, JNK, and p38 activation. Treatment of OASF with TNF‐α also increased the accumulation of phosphorylated c‐Jun in the nucleus, AP‐1‐luciferase activity, and c‐Jun binding to the AP‐1 element on the CCL2 promoter. TNF‐α‐mediated AP‐1‐luciferase activity and c‐Jun binding to the AP‐1 element were inhibited by TNFR1 Ab, thioredoxin, SP600125, and SB203580. Our results suggest that the interaction between TNF‐α and TNFR1 increases CCL2 expression in human synovial fibroblasts via the ASK1, JNK/p38, c‐Jun, and AP‐1 signaling pathway. J. Cell. Biochem. 113: 3509–3519, 2012. © 2012 Wiley Periodicals, Inc.