Altered expression of neuroplasticity-related genes in the brain of depressed suicides

Background: Expression of the neuronal membrane glycoprotein M6a (GPM6A), the proteolipid protein (PLP/DM20) family member, is downregulated in the hippocampus of chronically stressed animals. Its neuroplastic function involves a role in neurite formation, filopodium outgrowth and synaptogenesis through an unknown mechanism. Disruptions in neuroplasticity mechanisms have been shown to play a significant part in the etiology of depression. Thus, the current investigation examined whether GPM6A expression is also altered in human depressed brain. Methods: Expression levels and coexpression patterns of GPM6A, GPM6B, and PLP1 (two other members of PLP/DM20 family) as well as of the neuroplasticity-related genes identified to associate with GPM6A were determined using quantitative polymerase chain reaction (qPCR) in postmortem samples from the hippocampus (. n=. 18) and the prefrontal cortex (PFC) (. n=. 25) of depressed suicide victims and compared with control subjects (hippocampus n=. 18; PFC n=. 25). Neuroplasticity-related proteins that form complexes with GPM6A were identified by coimmunoprecipitation technique followed by mass spectrometry. Results: Results indicated transcriptional downregulation of GPM6A and GPM6B in the hippocampus of depressed suicides. The expression level of calcium/calmodulin-dependent protein kinase II alpha (CAMK2A) and coronin1A (CORO1A) was also significantly decreased. Subsequent analysis of coexpression patterns demonstrated coordinated gene expression in the hippocampus and in the PFC indicating that the function of these genes might be coregulated in the human brain. However, in the brain of depressed suicides this coordinated response was disrupted. Conclusions: Disruption of coordinated gene expression as well as abnormalities in GPM6A and GPM6B expression and expression of the components of GPM6A complexes were detected in the brain of depressed suicides.Fil: Fuchsova, Beata. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; ArgentinaFil: Alvarez Juliá, Anabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; ArgentinaFil: Rizavi, H. S.. University of Illinois; Estados UnidosFil: Frasch, Alberto Carlos C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; ArgentinaFil: Pandey, G. N.. University of Illinois; Estados Unido

Multi-component gap solitons in spinor Bose-Einstein condensates

We model the nonlinear behaviour of spin-1 Bose-Einstein condensates (BECs) with repulsive spin-independent interactions and either ferromagnetic or anti-ferromagnetic (polar) spin-dependent interactions, loaded into a one-dimensional optical lattice potential. We show that both types of BECs exhibit dynamical instabilities and may form spatially localized multi-component structures. The localized states of the spinor matter waves take the form of vector gap solitons and self-trapped waves that exist only within gaps of the linear Bloch-wave band-gap spectrum. Of special interest are the nonlinear localized states that do not exhibit a common spatial density profile shared by all condensate components, and consequently cannot be described by the single mode approximation (SMA), frequently employed within the framework of the mean-field treatment. We show that the non-SMA states can exhibits Josephson-like internal oscillations and self-magnetisation, i.e. intrinsic precession of the local spin. Finally, we demonstrate that non-stationary states of a spinor BEC in a lattice exhibit coherent undamped spin-mixing dynamics, and that their controlled conversion into a stationary state can be achieved by the application of an external magnetic field.Comment: 12 pages, 13 figure

Is children's weight a public health or a private family issue?:A qualitative analysis of online discussion about National Child Measurement Programme feedback in England 11 Medical and Health Sciences 1117 Public Health and Health Services

BACKGROUND: The National Child Measurement Programme (NCMP) is a child weight monitoring system in England, taking place in the first and final years of primary school. Many local authorities consider it important to inform parents if their child is overweight, and do so by letter alongside the offer of support and advice. Such letters have been met with mixed reactions from parents, but research seeking to better understand parents' responses is often limited by reliance on survey data and low participation rates. This study aimed to collect a broad variety of perspectives on the programme by analyzing views expressed in parent-to-parent discussions posted online.METHODS: UK-based online parenting fora were used to identify discussion threads based around the NCMP between 2010 and 2017. Thirty-one discussion threads from two parent fora were identified. Thematic analysis was used to identify themes in these data.RESULTS: The primary themes identified related to (1) the legitimacy of feedback and judgement from health professionals, (2) the relative importance of collecting population level data above individual preferences, and (3) risks versus benefits of having conversations with children about weight. Most threads adopted an 'argument, counter-argument' format, providing two sides to each issue raised. Information and opinions consistent with public health messages were frequently provided, such as how data are used, that feedback is intended to be helpful, and the importance of collecting national data. There was little evidence of individual parents shifting their views in response to others' arguments.CONCLUSIONS: This study provides novel insight into peer-to-peer debates about the NCMP, including the arguments parents find convincing and acceptable for and against a national programme to weigh children and provide feedback to parents about their weight. Online fora were used as an opportunity to express criticism or distress, but also to seek advice from peers regarding concerns about whether or not to opt-out. Thus, both general issues related to the legitimacy of population screening and outcomes for individual children were of concern to parents.</p

Online Faculty Professional Development and Community as Nexus

Our goal is to share ideas and experiences related to the design of dynamic, interactive professional development opportunities that focus on learning skills for managing remote or online teaching but more importantly that create a relationship-rich sense of community. Our Honors International Faculty Learning Online (HIFLO) model is a successful example in honors, but it offers reasonably adaptable strategies that can be used in future virtual professional development ventures inside or outside of honors. No matter what other topics may be addressed in later Honors International Faculty Institute (HIFI) or HIFLO seminars, the essential principle of community will always be a vital component

Excitons in InGaAs Quantum Dots without Electron Wetting Layer States

The Stranski-Krastanov (SK) growth-mode facilitates the self-assembly of quantum dots (QDs) using lattice-mismatched semiconductors, for instance InAs and GaAs. SK QDs are defect-free and can be embedded in heterostructures and nano-engineered devices. InAs QDs are excellent photon emitters: QD-excitons, electron-hole bound pairs, are exploited as emitters of high quality single photons for quantum communication. One significant drawback of the SK-mode is the wetting layer (WL). The WL results in a continuum rather close in energy to the QD-confined-states. The WL-states lead to unwanted scattering and dephasing processes of QD-excitons. Here, we report that a slight modification to the SK-growth-protocol of InAs on GaAs -- we add a monolayer of AlAs following InAs QD formation -- results in a radical change to the QD-excitons. Extensive characterisation demonstrates that this additional layer eliminates the WL-continuum for electrons enabling the creation of highly charged excitons where up to six electrons occupy the same QD. Single QDs grown with this protocol exhibit optical linewidths matching those of the very best SK QDs making them an attractive alternative to standard InGaAs QDs

Intestinal dendritic cells specialize to activate transforming growth factor-β and induce Foxp3+ regulatory T cells via integrin αvβ8

BACKGROUND & AIMS: The intestinal immune system is tightly regulated to prevent responses against the many nonpathogenic antigens in the gut. Transforming growth factor (TGF)-β is a cytokine that maintains intestinal homeostasis, in part by inducing Foxp3(+) regulatory T cells (Tregs) that suppress immune responses. TGF-β is expressed at high levels in the gastrointestinal tract as a latent complex that must be activated. However, the pathways that control TGF-β activation in the intestine are poorly defined. We investigated the cellular and molecular pathways that control activation of TGF-β and induction of Foxp3(+) Tregs in the intestines of mice to maintain immune homeostasis. METHODS: Subsets of intestinal dendritic cells (DCs) were examined for their capacity to activate TGF-β and induce Foxp3(+) Tregs in vitro. Mice were fed oral antigen, and induction of Foxp3(+) Tregs was measured. RESULTS: A tolerogenic subset of intestinal DCs that express CD103 were specialized to activate latent TGF-β, and induced Foxp3(+) Tregs independently of the vitamin A metabolite retinoic acid. The integrin αvβ8, which activates TGF-β, was significantly up-regulated on CD103(+) intestinal DCs. DCs that lack expression of integrin αvβ8 had reduced ability to activate latent TGF-β and induce Foxp3(+) Tregs in vitro and in vivo. CONCLUSIONS: CD103(+) intestinal DCs promote a tolerogenic environment in the intestines of mice via integrin αvβ8-mediated activation of TGF-β

Binary Local Fractal Dimension: a Precise Structure Parameter for 3D High Resolution Computed Tomography Images of the Human Spongiosa

We present the Binary Local Fractal Dimension (LFD) to analyze osteoporosis induced fracture risk with clinical 3D high resolution quantitative computed tomographic (HRCT) images of human vertebrae. We test if LFD parameters provide precise additional information besides bone mineral density (BMD) and standard descriptors of bone quality, for example bone surface ratio (BS/BV). We define a weighted LFD (wLFD) using the ¯R2 of the H¨older exponents. We compare the LFD with standard methods (distance transform, direct secant method and run-length method) on 5 vertebrae × 8 volumes of interest and 5 repeated scans. The wLFD contains the highest direct and BMD-independent precision (R2 = 0.985 and R2 = 0.949), followed by BS/BV (R2 = 0.977 and R2 = 0.920) including low correlation with BMD (wLFD: R2 = 0.704, BS/BV: R2 = 0.814). LFD improves the translation from reference μCT- to clinical HRCT-resolution. In conclusion, LFD provides a strong diagnostic tool to characterize bone quality to predict osteoporosis induced fracture risk.Sociedad Argentina de Informática e Investigación Operativ

Alanine Scanning Mutagenesis of the C-Terminal Cytosolic End of Gpm6a Identifies Key Residues Essential for the Formation of Filopodia

Neuronal membrane glycoprotein M6a (Gpm6a) is a protein with four transmembrane regions and the N- and the C-ends facing the cytosol. It functions in processes of neuronal development, outgrowth of neurites, and formation of filopodia, spines, and synapsis. Molecular mechanisms by which Gpm6a acts in these processes are not fully comprehended. Structural similarities of Gpm6a with tetraspanins led us to hypothesize that, similarly to tetraspanins, the cytoplasmic tails function as connections with cytoskeletal and/or signaling proteins. Here, we demonstrate that the C- but not the N-terminal cytosolic end of Gpm6a is required for the formation of filopodia by Gpm6a in cultured neurons from rat hippocampus and in neuroblastoma cells N2a. Further immunofluorescence microcopy and flow cytometry analysis show that deletion of neither the N- nor the C-terminal intracellular domains interferes with the recognition of Gpm6a by the function-blocking antibody directed against the extracellular part of Gpm6a. Expression levels of both truncation mutants were not affected but we observed decrease in the amount of both truncated proteins on cell surface suggesting that the incapacity of the Gpm6a lacking C-terminus to induce filopodium formation is not due to the lower amount of Gpm6a on cell surface. Following colocalization assays shows that deletion of the C- but not the N-terminus diminishes the association of Gpm6a with clathrin implying involvement of clathrin-mediated trafficking events. Next, using comprehensive alanine scanning mutagenesis of the C-terminus we identify K250, K255, and E258 as the key residues for the formation of filopodia by Gpm6a. Substitution of these charged residues with alanine also diminishes the amount of Gpm6a on cell surface and in case of K255 and E258 leads to the lower amount of total expressed protein. Subsequent bioinformatic analysis of Gpm6a amino acid sequence reveals that highly conserved and functional residues cluster preferentially within the C- and not within the N-terminus and that K250, K255, and E258 are predicted as part of sorting signals of transmembrane proteins. Altogether, our results provide evidence that filopodium outgrowth induced by Gpm6a requires functionally critical residues within the C-terminal cytoplasmic tail.Fil: Rosas, Nicolás Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Alvarez Juliá, Anabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Alzuri, Sofia E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Frasch, Alberto Carlos C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Fuchsova, Beata. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentin

Binary Local Fractal Dimension: a Precise Structure Parameter for 3D High Resolution Computed Tomography Images of the Human Spongiosa

We present the Binary Local Fractal Dimension (LFD) to analyze osteoporosis induced fracture risk with clinical 3D high resolution quantitative computed tomographic (HRCT) images of human vertebrae. We test if LFD parameters provide precise additional information besides bone mineral density (BMD) and standard descriptors of bone quality, for example bone surface ratio (BS/BV). We define a weighted LFD (wLFD) using the ¯R2 of the H¨older exponents. We compare the LFD with standard methods (distance transform, direct secant method and run-length method) on 5 vertebrae × 8 volumes of interest and 5 repeated scans. The wLFD contains the highest direct and BMD-independent precision (R2 = 0.985 and R2 = 0.949), followed by BS/BV (R2 = 0.977 and R2 = 0.920) including low correlation with BMD (wLFD: R2 = 0.704, BS/BV: R2 = 0.814). LFD improves the translation from reference μCT- to clinical HRCT-resolution. In conclusion, LFD provides a strong diagnostic tool to characterize bone quality to predict osteoporosis induced fracture risk.Sociedad Argentina de Informática e Investigación Operativ