Developmental Changes in the Structure and Composition of the Postsynaptic Density

The development of the brain and its underlying circuitry is dependent on the formation of trillions of chemical synapses, which are highly specialized contacts that regulate the flow of information from one neuron to the next. It is through these synaptic connections that neurons wire together into networks capable of performing specific tasks, and activity-dependent changes in their structural and physiological state is one way that the brain is thought to adapt and store information. At the ultrastructural level, developmental and activity-dependent changes in the size and shape of dendritic spines have been well documented, and it is widely believed that structural changes in spines are a hallmark sign of synapse maturation and alteration of synaptic physiology. While changes in spine structure have been studied extensively, changes in one of its most prominent components, the postsynaptic density (PSD), have largely evaded observation. The PSD is a protein-rich organelle on the cytoplasmic side of the postsynaptic membrane, where it sits in direct opposition to the presynaptic terminal. The PSD functions both to cluster neurotransmitter receptors at the cell surface as well as organize the intracellular signaling molecules responsible for transducing extracellular signals to the postsynaptic cell. Much is known about the chemical composition of the PSD, but the structural arrangement of its molecular components is not well documented. Adding to the difficulty of understanding such a complex mass of protein machinery is the fact that its protein composition is known to change in response to synaptic activity, meaning that its structure is plastic and no two PSDs are identical. Here, immuno-gold labeling and electron tomography of PSDs isolated throughout development was used to track changes in both the structure and molecular composition of the PSD. State-of-the-art cryo-electron tomography was used to study the fine structure of the PSD during development, and provides an unprecedented glimpse into its molecular architecture in an un-fixed, unstained and hydrated state. Through this analysis, large structural and compositional changes are apparent and suggest a model by which the PSD is first assembled as a mesh-like lattice of proteins that function as support for the later recruitment of various PSD components. Spatial analysis of the recruitment of proteins into the PSD demonstrated that its assembly has an underlying order.

Effects of anticancer drug docetaxel on the structure and function of the rabbit olfactory mucosa

Docetaxel (DCT) is an anticancer drug which acts by disrupting microtubule dynamics in the highly mitotic cancer cells. Thus, this drug has a potential to affect function and organization of tissues exhibiting high cellular turnover. We investigated, in the rabbit, the effects of a single human equivalent dose (6.26mg/kg, i.v.) of DCT on the olfactory mucosa (OM) through light and electron microscopy, morphometry, Ki-67 immunostaining, TUNEL assay and the buried food test for olfactory sensitivity. On post-exposure days (PED) 5 and 10, there was disarrangement of the normal cell layering in the olfactory epithelium (OE), apoptotic death of cells of the OE, Bowman's glands and axon bundles, and the presence (including on PED 3) of blood vessels in the bundle cores. A decrease in bundle diameters, olfactory cell densities and cilia numbers, which was most significant on PED 10 (49.3%, 63.4% and 50%, respectively), was also evident. Surprisingly by PED 15, the OM regained normal morphology. Furthermore, olfactory sensitivity decreased progressively until PED 10 when olfaction was markedly impaired, and with recovery from the impairment by PED 15. These observations show that DCT transiently alters the structure and function of the OM suggesting a high regenerative potential for this tissue.

Sheaf representations of MV-algebras and lattice-ordered abelian groups via duality

We study representations of MV-algebras -- equivalently, unital lattice-ordered abelian groups -- through the lens of Stone-Priestley duality, using canonical extensions as an essential tool. Specifically, the theory of canonical extensions implies that the (Stone-Priestley) dual spaces of MV-algebras carry the structure of topological partial commutative ordered semigroups. We use this structure to obtain two different decompositions of such spaces, one indexed over the prime MV-spectrum, the other over the maximal MV-spectrum. These decompositions yield sheaf representations of MV-algebras, using a new and purely duality-theoretic result that relates certain sheaf representations of distributive lattices to decompositions of their dual spaces. Importantly, the proofs of the MV-algebraic representation theorems that we obtain in this way are distinguished from the existing work on this topic by the following features: (1) we use only basic algebraic facts about MV-algebras; (2) we show that the two aforementioned sheaf representations are special cases of a common result, with potential for generalizations; and (3) we show that these results are strongly related to the structure of the Stone-Priestley duals of MV-algebras. In addition, using our analysis of these decompositions, we prove that MV-algebras with isomorphic underlying lattices have homeomorphic maximal MV-spectra. This result is an MV-algebraic generalization of a classical theorem by Kaplansky stating that two compact Hausdorff spaces are homeomorphic if, and only if, the lattices of continuous [0, 1]-valued functions on the spaces are isomorphic.

A Cruciform Electron Donor-Acceptor Semiconductor with Solid-State Red Emission: 1D/2D Optical Waveguides and Highly Sensitive/Selective Detection of H2S Gas

In this paper, a new cruciform donor–acceptor molecule 2,2'-((5,5'-(3,7-dicyano-2,6-bis(dihexylamino)benzo[1,2-b:4,5-b']difuran-4,8-diyl)bis(thiophene-5,2-diyl))bis (methanylylidene))dimalononitrile (BDFTM) is reported. The compound exhibits both remarkable solid-state red emission and p-type semiconducting behavior. The dual functions of BDFTM are ascribed to its unique crystal structure, in which there are no intermolecular face-to-face π–π interactions, but the molecules are associated by intermolecular CN…π and H-bonding interactions. Firstly, BDFTM exhibits aggregation-induced emission; that is, in solution, it is almost non-emissive but becomes significantly fluorescent after aggregation. The emission quantum yield and average lifetime are measured to be 0.16 and 2.02 ns, respectively. Crystalline microrods and microplates of BDFTM show typical optical waveguiding behaviors with a rather low optical loss coefficient. Moreover, microplates of BDFTM can function as planar optical microcavities which can confine the emitted photons by the reflection at the crystal edges. Thin films show an air-stable p-type semiconducting property with a hole mobility up to 0.0015 cm2V−1s−1. Notably, an OFET with a thin film of BDFTM is successfully utilized for highly sensitive and selective detection of H2S gas (down to ppb levels).

Crystal structure of the sodium-proton antiporter NhaA dimer and new mechanistic insights

Sodium-proton antiporters rapidly exchange protons and sodium ions across the membrane to regulate intracellular pH, cell volume, and sodium concentration. How ion binding and release is coupled to the conformational changes associated with transport is not clear. Here, we report a crystal form of the prototypical sodium-proton antiporter NhaA from Escherichia coli in which the protein is seen as a dimer. In this new structure, we observe a salt bridge between an essential aspartic acid (Asp163) and a conserved lysine (Lys300). An equivalent salt bridge is present in the homologous transporter NapA, but not in the only other known crystal structure of NhaA, which provides the foundation of most existing structural models of electrogenic sodium-proton antiport. Molecular dynamics simulations show that the stability of the salt bridge is weakened by sodium ions binding to Asp164 and the neighboring Asp163. This suggests that the transport mechanism involves Asp163 switching between forming a salt bridge with Lys300 and interacting with the sodium ion. pKa calculations suggest that Asp163 is highly unlikely to be protonated when involved in the salt bridge. As it has been previously suggested that Asp163 is one of the two residues through which proton transport occurs, these results have clear implications to the current mechanistic models of sodium-proton antiport in NhaA.

The Structure and Correlates of Self-Reported DSM-5 Maladaptive Personality Traits: Findings From Two German-Speaking Samples

The authors investigated the structure and correlates of DSM-5 maladaptive personality traits in two samples of 577 students and 212 inpatients using the German self-report form of the Personality Inventory for DSM-5. They found that (a) the factor structure of DSM-5 trait facets is largely in line with the proposed trait domains of Negative Affectivity, Detachment, Antagonism, Disinhibition, and Psychoticism; (b) all DSM-5 trait domains except Psychoticism are highly related to the respective domains of the Five-Factor Model of personality; (c) the trait facets are positively associated with a self-report measure of general personality dysfunction; and (d) the DSM-5 trait facets show differential associations with a range of self-reported DSM-IV Axis I disorders. These findings give further support to the new DSM-5 trait model and suggest that it may generalize to other languages and cul

Trypanosoma brucei RRM1 is a nuclear RNA-binding protein and modulator of chromatin structure

TbRRM1 of Trypanosoma brucei is a nucleoprotein that was previously identified in a search for splicing factors in T. brucei. We show that TbRRM1 associates with mRNAs and with the auxiliary splicing factor polypyrimidine tract-binding protein 2, but not with components of the core spliceosome. TbRRM1 also interacts with several retrotransposon hot spot (RHS) proteins and histones. RNA immunoprecipitation of a tagged form of TbRRM1 from procyclic (insect) form trypanosomes identified ca. 1,500 transcripts that were enriched and 3,000 transcripts that were underrepresented compared to cellular mRNA. Enriched transcripts encoded RNA-binding proteins, including TbRRM1 itself, several RHS transcripts, mRNAs with long coding regions, and a high proportion of stage-regulated mRNAs that are more highly expressed in bloodstream forms. Transcripts encoding ribosomal proteins, other factors involved in translation, and procyclic-specific transcripts were underrepresented. Knockdown of TbRRM1 by RNA interference caused widespread changes in mRNA abundance, but these changes did not correlate with the binding of the protein to transcripts, and most splice sites were unchanged, negating a general role for TbRRM1 in splice site selection. When changes in mRNA abundance were mapped across the genome, regions with many downregulated mRNAs were identified. Two regions were analyzed by chromatin immunoprecipitation, both of which exhibited increases in nucleosome occupancy upon TbRRM1 depletion. In addition, subjecting cells to heat shock resulted in translocation of TbRRM1 to the cytoplasm and compaction of chromatin, consistent with a second role for TbRRM1 in modulating chromatin structure. IMPORTANCE: Trypanosoma brucei, the parasite that causes human sleeping sickness, is transmitted by tsetse flies. The parasite progresses through different life cycle stages in its two hosts, altering its pattern of gene expression in the process. In trypanosomes, protein-coding genes are organized as polycistronic units that are processed into monocistronic mRNAs. Since genes in the same unit can be regulated independently of each other, it is believed that gene regulation is essentially posttranscriptional. In this study, we investigated the role of a nuclear RNA-binding protein, TbRRM1, in the insect stage of the parasite. We found that TbRRM1 binds nuclear mRNAs and also affects chromatin status. Reduction of nuclear TbRRM1 by RNA interference or heat shock resulted in chromatin compaction. We propose that TbRRM1 regulates RNA polymerase II-driven gene expression both cotranscriptionally, by facilitating transcription and efficient splicing, and posttranscriptionally, via its interaction with nuclear mRNAs.

Primary structure and evolutionary relationship between the adult alpha-globin genes and their 5'-flanking regions of Xenopus laevis and Xenopus tropicalis

To investigate the evolution of globin genes in the genus Xenopus, we have determined the primary structure of the related adult alpha I- and alpha II-globin genes of X. laevis and of the adult alpha-globin gene of X. tropicalis, including their 5'-flanking regions. All three genes are comprised of three exons and two introns at homologous positions. The exons are highly conserved and code for 141 amino acids. By contrast, the corresponding introns vary in length and show considerable divergence. Comparison of 900 bp of the 5'-flanking region revealed that the X. tropicalis gene contains a conserved proximal 310-bp promoter sequence, comprised of the canonical TATA and CCAAT motifs at homologous positions, and five conserved elements in the same order and at similar positions as previously shown for the corresponding genes of X. laevis. We therefore conclude that these conserved upstream elements may represent regulatory sequences for cell-specific regulation of the adult Xenopus globin genes.

The impact of the position effect on the factorial structure of the Culture Fair Test (CFT)

The Culture Fair Test (CFT) is a psychometric test of fluid intelligence consisting of four subtests; Series, Classification, Matrices, and Topographies. The four subtests are only moderately intercorrelated, doubting the notion that they assess the same construct (i.e., fluid intelligence). As an explanation of these low correlations, we investigated the position effect. This effect is assumed to reflect implicit learning during testing. By applying fixed-links modeling to analyze the CFT data of 206 participants, we identified position effects as latent variables in the subtests; Classification, Matrices, and Topographies. These position effects were disentangled from a second set of latent variables representing fluid intelligence inherent in the four subtests. After this separation of position effect and basic fluid intelligence, the latent variables representing basic fluid intelligence in the subtests Series, Matrices, and Topographies could be combined to one common latent variable which was highly correlated with fluid intelligence derived from the subtest Classification (r=.72). Correlations between the three latent variables representing the position effects in the Classification, Matrices, and Topographies subtests ranged from r=.38 to r=.59. The results indicate that all four CFT subtests measure the same construct (i.e., fluid intelligence) but that the position effect confounds the factorial structure

Structure-function analysis of human Integrator subunit-4

Structure-function analysis of human Integrator subunit 4 Anupama Sataluri Advisor: Eric. J. Wagner, Ph.D. Uridine-rich small nuclear RNAs (U snRNA) are RNA Polymerase-II (RNAPII) transcripts that are ubiquitously expressed and are known to be essential for gene expression. snRNAs play a key role in mRNA splicing and in histone mRNA expression. Inaccurate snRNA biosynthesis can lead to diseases related to defective splicing and histone mRNA expression. Although the 3′ end formation mechanism and processing machinery of other RNAPII transcripts such as mRNA has been well studied, the mechanism of snRNA 3′ end processing has remained a mystery until the recent discovery of the machinery that mediates this process. In 2005, a complex of 14 subunits (the Integrator complex) associated with RNA Polymerase-II was discovered. The 14subunits were annotated Integrator 1-14 based on their size. The subunits of this complex together were found to facilitate 3′ end processing of snRNA. Identification of the Integrator complex propelled research in the direction of understanding the events of snRNA 3’end processing. Recent studies from our lab confirmed that Integrator subunit (IntS) 9 and 11 together perform the endonucleolytic cleavage of the nascent snRNA 3′ end to generate mature snRNA. However, the role of other members of the Integrator complex remains elusive. Current research in our lab is focused on deciphering the role of each subunit within the Integrator complex This work specifically focuses on elucidating the role of human Integrator subunit 4 (IntS4) and understanding how it facilitates the overall function of the complex. IntS4 has structural similarity with a protein called “Symplekin”, which is part of the mRNA 3’end processing machinery. Symplekin has been thoroughly researched in recent years and structure-function correlation studies in the context of mRNA 3’end processing have reported a scaffold function for Symplekin due to the presence of HEAT repeat motifs in its N-terminus. Based upon the structural similarity between IntS4 and Symplekin, we hypothesized that Integrator subunit 4 may be behaving as a Symplekin-like scaffold molecule that facilitates the interaction between other members of the Integrator Complex. To answer this question, the two important goals of this study were to: 1) identify the region of IntS4, which is important for snRNA 3′ end processing and 2) determine binding partners of IntS4 which promote its function as a scaffold. IntS4 structurally consists of a highly conserved N-terminus with 8 HEAT repeats, followed by a nonconserved C- terminus. A series of siRNA resistant N and C-terminus deletion constructs as well as specific point mutants within its N-terminal HEAT repeats were generated for human IntS4 and, utilizing a snRNA transcriptional readthrough GFP-reporter assay, we tested their ability to rescue misprocessing. This assay revealed a possible scaffold like property of IntS4. To probe IntS4 for interaction partners, we performed co-immunoprecipitation on nuclear extracts of IntS4 expressing stable cell lines and identified IntS3 and IntS5 among other Integrator subunits to be binding partners which facilitate the scaffold like function of hIntS4. These findings have established a critical role for IntS4 in snRNA 3′ end processing, identified that both its N and C termini are essential for its function, and mapped putative interaction domains with other Integrator subunits.

Value added trade and structure of high-technology exports in China

This study focuses on the technological intensity of China's exports. It first introduces the method of decomposing gross exports by using the Asian international input–output tables. The empirical results indicate that the technological intensity of Chinese exports has been significantly overestimated due to its high dependency on import content, especially in high-technology exports, an area highly dominated by the electronic and electrical equipment sector. Furthermore, a significant portion of value added embodied in China's high-technology exports comes from services and high-technology manufacturers in neighboring economies, such as Japan, South Korea, and Taiwan.

Topological invariance and spatial scaling of surface roughness in two highly eroded zones of Mexico: a comparative study

The Fractal Image Informatics toolbox (Oleschko et al., 2008 a; Torres-Argüelles et al., 2010) was applied to extract, classify and model the topological structure and dynamics of surface roughness in two highly eroded catchments of Mexico. Both areas are affected by gully erosion (Sidorchuk, 2005) and characterized by avalanche-like matter transport. Five contrasting morphological patterns were distinguished across the slope of the bare eroded surface of Faeozem (Queretaro State) while only one (apparently independent on the slope) roughness pattern was documented for Andosol (Michoacan State). We called these patterns ?the roughness clusters? and compared them in terms of metrizability, continuity, compactness, topological connectedness (global and local) and invariance, separability, and degree of ramification (Weyl, 1937). All mentioned topological measurands were correlated with the variance, skewness and kurtosis of the gray-level distribution of digital images. The morphology0 spatial dynamics of roughness clusters was measured and mapped with high precision in terms of fractal descriptors. The Hurst exponent was especially suitable to distinguish between the structure of ?turtle shell? and ?ramification? patterns (sediment producing zone A of the slope); as well as ?honeycomb? (sediment transport zone B) and ?dinosaur steps? and ?corals? (sediment deposition zone C) roughness clusters. Some other structural attributes of studied patterns were also statistically different and correlated with the variance, skewness and kurtosis of gray distribution of multiscale digital images. The scale invariance of classified roughness patterns was documented inside the range of five image resolutions. We conjectured that the geometrization of erosion patterns in terms of roughness clustering might benefit the most semi-quantitative models developed for erosion and sediment yield assessments (de Vente and Poesen, 2005).

Caracterización y aprovechamiento de los varillales amazónicos : contribución a la economía de las comunidades locales

La Gestión Forestal Sustentable es la principal herramienta para garantizar la compatibilidad entre producción y conservación en todos los bosques, y mas especialmente en los que exhiben niveles máximos de diversidad, como los tropicales humedos. En ellos existe un gran desconocimiento sobre la gestión de los recursos maderables de pequeña dimensión y los no maderables (PFNM) con mercado local. La madera redonda de pequeño diámetro es un recurso forestal de bajo valor económico extraído tradicionalmente por los pobladores locales de las zonas tropicales húmedas para construir sus viviendas. Los fustes de mejor calidad se obtienen del bosque de varillal, o bosques sobre arena blanca, altamente oligotroficos, sin potencial agrícola, escasos, dispersos, de pequeña superficie, gran fragilidad y alto porcentaje de endemismos. En el entorno de los centros urbanos de la Amazonia peruana, esta madera supone uno de los principales ingresos económicos para la población local, al ser extraida para su comercialización en dichos centros urbanos. Esto supone un riesgo de sobre-explotacion cuyos efectos se desconocen hasta el momento. Para acercarnos la situacion ambiental, social y económica asociada al varillal, se han realizado inventarios botanicos y de estructura forestal, se ha descrito el sistema de aprovechamiento tradicional y cuantificado sus efectos y, finalmente, se han realizado encuestas orientadas a analizar la situación social y economica de las comunidades locales que extraen y comercializan sus productos. El aprovechamiento tradicional del varillal es una actividad de bajo impacto que no emplea maquinaria y se centra en la extracción de fustes con diámetro normal entre 5 y 15 cm y características especificas de longitud, forma de fuste y calidad de la especie. Los resultados ponen de manifiesto la relevancia de la distancia existente entre el punto de extracción y el punto de venta, asi como la gran influencia que tiene la situación social y económica en la gestión sustentable del varillal. Todo ello pone en evidencia que si existe un cierto efecto negativo de la extracción intensa y continuada que han sufrido los varíllales mas próximos al centro urbano. Para favorecer una Gestión Forestal Sustentable que reduzca este efecto negativo es esencial llevar a cabo una adecuada planificación comunal que permita establecer una secuencia ordenada de zonas de corta y un cronograma para su gestión y aprovechamiento que evite la extracción repetida en un mismo varillal. ABSTRACT Sustainable forest management is the main tool to ensure compatibility between production and conservation in all forests, and especially in those exhibiting the maximum levels of diversity, such as tropical rain. Within them there is a great ignorance about the management of small sized timber and non-timber resources (PFMN) in the local market. The small-diameter round timber is a forest resource of low economic value extracted traditionally by local people of the humid tropics to build their homes. The better quality shafts are obtained from varillal forest or forests on white sand, highly oligotrophic, no agricultural potential, few, scattered, small size, fragility and high percentage of endemic species. In the environment of the urban centres of the Peruvian Amazon, this wood is one of the main incomes for the local population, since it is extracted for marketing in these urban centres. This poses a risk of overexploitation whose effects are unknown so far. To approach the environmental, social and economic situation associated to the varillal, botanical and forest structure inventories have been conducted, traditional harvesting systems described and their effects quantified and targeted surveys have eventually been conducted to analyse the social and local economic situation of the communities that extract and sell the products. The traditional use of varillal is a low-impact activity that does not use machinery and focuses on the extraction of shafts with a normal diameter of between 5 and 15 cm and specific characteristics in length, stem form and quality of the species. The results highlight the importance of the distance from the extraction point and the sale point, and the great influence of the social and economic situation in the sustainable management of varillal. This demonstrates that there is indeed a negative effect caused by the intense and continuous extraction that varillales closest to the city centre have suffered. To encourage a Sustainable Forest Management to reduce this negative effect is essential to conduct proper community planning in order to establish an ordered sequence of areas and a chronogram for their management and use, to avoid a repeat extraction in the same varillal.

Effect of misorientation on the compression of highly anisotropic single-crystal micropillars

The effect of crystal misorientation, geometrical tilt, and contact misalignment on the compression of highly anisotropic single crystal micropillars was assessed by means of crystal plasticity finite element simulations. The investigation was focused in single crystals with the NaCl structure, like MgO or LiF, which present a marked plastic anisotropy as a result of the large difference in the critical resolved shear stress between the “soft” {110}〈110〉 and the “hard” {100}〈110〉 active slip systems. It was found that contact misalignment led to a large reduction in the initial stiffness of the micropillar in crystals oriented in the soft and hard direction. The crystallographic tilt did not modify, however, the initial crystal stiffness. From the viewpoint of the plastic response, none of the effects analyzed led to significant differences in the flow stress when the single crystals were oriented along the “soft” [100] direction. Large differences were found, however, if the single crystal was oriented in the “hard” [111] direction as a result of the activation of the soft slip system. Numerical simulations were in very good agreement with experimental literature data.

Highly conductive coatings of carbon black/silica composites obtained by a sol-gel process

Conductive submicronic coatings of carbon black (CB)/silica composites have been prepared by a sol-gel process and deposited by spray-coating on glazed porcelain tiles. Stable CB dispersions with surfactant were rheologically characterized to determine the optimum CB-surfactant ratio. The composites were analyzed by Differential Thermal and Thermogravimetric Analysis and Hg-Porosimetry. Thin coatings were thermally treated in the temperature range of 300-500degC in air atmosphere. The microstructure of the coatings was determined by scanning electron microscopy and the structure evaluated by confocal Raman spectroscopy. The electrical characterization of the samples was carried out using dc intensity-voltage curves. The coatings exhibit good adhesion, high density and homogeneous distribution of the conductive filler (CB) in the insulate matrix (silica) that protects against the thermal degradation of the CB nanoparticles during the sintering process. As consequence, the composite coatings show the lowest resistivity values for CB-based films reported in the literature, with values of ~7times10 -5Omegam.