The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

Design and Characterization of an Electrically Powered Single Molecule on Gold

The surface diffusion of individual molecules is of paramount importance in self-assembly processes and catalytic processes. However, the fundamental understanding of molecule diffusion peculiarities considering conformations and adsorption sites remain poorly known at the atomic scale. Here, we probe the 4′-(4-tolyl)-2,2′:6′,2″-terpyridine adsorbed on the Au(111) herringbone structure combining scanning tunneling microscopy and atomic force microscopy. Molecules are controllably translated by electrons excitations over the reconstruction, except at elbows acting as pinning centers. Experimental data supported by theoretical calculations show the formation of coordination bonds between the molecule and Au atoms of the surface. Using force spectroscopy, we quantify local variation of the surface potential and the lateral force required to move the molecule. We found an elevation of the diffusion barrier at elbows of the reconstruction of ∼100 meV compared to the rest of the surface

Behavioral Consequences of NMDA Antagonist-Induced Neuroapoptosis in the Infant Mouse Brain

Background: Exposure to NMDA glutamate antagonists during the brain growth spurt period causes widespread neuroapoptosis in the rodent brain. This period in rodents occurs during the first two weeks after birth, and corresponds to the third trimester of pregnancy and several years after birth in humans. The developing human brain may be exposed to NMDA antagonists through drug-abusing mothers or through anesthesia. Methodology/Principal Findings: We evaluated the long-term neurobehavioral effects of mice exposed to a single dose of the NMDA antagonist, phencyclidine (PCP), or saline, on postnatal day 2 (P2) or P7, or on both P2 and P7. PCP treatment on P2 + P7 caused more severe cognitive impairments than either single treatment. Histological examination of acute neuroapoptosis resulting from exposure to PCP indicated that the regional pattern of degeneration induced by PCP in P2 pups was different from that in P7 pups. The extent of damage when evaluated quantitatively on P7 was greater for pups previously treated on P2 compared to pups treated only on P7. Conclusions: These findings signify that PCP induces different patterns of neuroapoptosis depending on the developmental age at the time of exposure, and that exposure at two separate developmental ages causes more severe neuropathologica

Genetic Variants For Head Size Share Genes and Pathways With Cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer

Clinical evaluation of two immunoassay methods for the rapid detection of chlamydia trachomatis : antigen in endocervical specimens from high risk female patients

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenTwo rapid immunoassay methods, QuickVue-Chlamydia (Quidel Corp., San Diego California) and Kodak Surecell (Kodak Corp. Rochester, N.Y.) were evaluated for the detection of Chlamydia trachomatis antigen in endocervical swabs from high risk females attending a sexually transmitted disease clinic. The results were compared to McCoy cell culture and a polymerase chain reaction assay (Amplicor®-PCR, Roche Molecular Systems). Of the 240 females enrolled in the study 45 were considered infected (18.8%). Sensitivity, specificity, predictive value of a positive (PVP) and predictive value of a negative (PVN) of the QuickVue-Chlamydia assay were 96%, 99%, 96% and 99% respectively. Sensitivity, specificity, PVP and PVN of the Surecell assay were 96%, 100%, 100% and 99% respectively. The performance of the two immunoassay methods was similar, the sensitivity was the same and the specificity of the Kodak Surecell was slightly better than that of the QuickVue. On the other hand, the QuickWVL&-Chlamydia assay was considerably simpler to perform (fewer steps) than the Kodak Surecell assay and took significantly less of technologists time

Clinical evaluation of two immunoassay methods for the rapid detection of chlamydia trachomatis : antigen in endocervical specimens from high risk female patients

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenTwo rapid immunoassay methods, QuickVue-Chlamydia (Quidel Corp., San Diego California) and Kodak Surecell (Kodak Corp. Rochester, N.Y.) were evaluated for the detection of Chlamydia trachomatis antigen in endocervical swabs from high risk females attending a sexually transmitted disease clinic. The results were compared to McCoy cell culture and a polymerase chain reaction assay (Amplicor®-PCR, Roche Molecular Systems). Of the 240 females enrolled in the study 45 were considered infected (18.8%). Sensitivity, specificity, predictive value of a positive (PVP) and predictive value of a negative (PVN) of the QuickVue-Chlamydia assay were 96%, 99%, 96% and 99% respectively. Sensitivity, specificity, PVP and PVN of the Surecell assay were 96%, 100%, 100% and 99% respectively. The performance of the two immunoassay methods was similar, the sensitivity was the same and the specificity of the Kodak Surecell was slightly better than that of the QuickVue. On the other hand, the QuickWVL&-Chlamydia assay was considerably simpler to perform (fewer steps) than the Kodak Surecell assay and took significantly less of technologists time

Transoid-to-Cisoid Conformation Changes of Single Molecules on Surfaces Triggered by Metal Coordination

Conformational isomers are stereoisomers that can interconvert over low potential barriers by rotation around a single bond. However, such bond rotation is hampered by geometrical constraints when molecules are adsorbed on surfaces. Here we show that the adsorption of 4,40-bis(4-carboxyphenyl)-6,60-dimethyl-2,20-bipyridine molecules on surfaces leads to the appearance of pro-chiral single-molecules on NiO(001) and to enantiopure supramolecular domains on Au(111) surfaces containing the transoid molecule conformation. Upon additional Fe adatom deposition, molecules undergo a controlled interconversion from a transoid to cisoid conformation as a result of coordination of the Fe atoms to the 2,20-bipyridine moieties. As confirmed by atomic force microscopy 1 images and X-ray photoelectron spectroscopy measurements, the resulting molecular structures become irreversibly achiral

Occurrence of minimal change nephrotic syndrome in classical Hodgkin lymphoma is closely related to the induction of c-mip in Hodgkin-Reed Sternberg cells and podocytes.

International audienceIt is currently considered that idiopathic minimal change nephrotic syndrome is an immune-mediated glomerular disease. Its association with classical Hodgkin lymphoma minimal change nephrotic syndrome (cHL-MCNS) suggests a molecular link, which remains to be elucidated. We analyzed the expression of cmaf inducing protein (c-mip) in lymphomatous tissues and kidney biopsy samples of patients with cHL-MCNS (n = 8) and in lymphomatous tissues of patients with isolated cHL (n = 9). Because c-mip affects the regulatory loop involving Fyn, we investigated possible structural defects in this signaling pathway, using laser capture microdissection, reverse transcription polymerase chain reaction, and Western blotting. We found that c-mip was selectively expressed in Hodgkin and Reed-Sternberg (HRS) cells and podocytes of patients with cHL-MCNS but is undetectable in patients with isolated cHL. We demonstrated that c-mip was specifically involved in the negative regulation of early proximal signaling through its interaction with phosphoprotein associated with glycosphingolipid-enriched microdomains and Fyn. We showed that the up-regulation of c-mip in cHL-MCNS was associated with a possible Fyn defect in HRS cells and podocytes. Moreover, we showed that c-mip was up-regulated in Fyn-deficient podocytes. c-mip may be a useful marker of cHL-MCNS and its induction reflects the dysregulation of proximal signaling