Dopamine D-2 up-regulation in psychosis patients after antipsychotic drug treatment

Purpose of reviewRecently, it has been questioned whether the re-emergence of psychotic symptoms following antipsychotic discontinuation or dose reduction is attributable to underlying psychotic vulnerability or to rebound effects of chronic use of antipsychotic medication. It was repeatedly shown that relapse rates are high after discontinuation of maintenance treatment. A potential contributing factor could be the increase in density of postsynaptic dopamine D2 receptors in the striatum and the higher affinity of D2 receptors for dopamine after chronic blockade.Recent findingsTo date, little clinical evidence is available for the mechanisms involved in postsynaptic striatal D2 receptor up-regulation after use of antipsychotic medication, and most knowledge comes from animal studies.SummaryFurther research is needed to investigate whether antipsychotic medication causes neuroadaptations leading to a dopamine supersensitive state in humans, how long such hypersensitive states may last and what differences exist between high and low D2 affinity antipsychotic drugs. Further, information is needed on discontinuation schedules that provide optimal protection for relapse during hypersensitive periods

Does Infall End Before the Class I Stage?

We have observed HCO+ J=3-2 toward 16 Class I sources and 18 Class 0 sources, many of which were selected from Mardones et al. (1997). Eight sources have profiles significantly skewed to the blue relative to optically thin lines. We suggest six sources as new infall candidates. We find an equal "blue excess" among Class 0 and Class I sources after combining this sample with that of Gregersen et al. (1997). We used a Monte Carlo code to simulate the temporal evolution of line profiles of optically thick lines of HCO+, CS and H2CO in a collapsing cloud and found that HCO+ had the strongest asymmetry at late times. If a blue-peaked line profile implies infall, then the dividing line between the two classes does not trace the end of the infall stage.Comment: 21 pages, 8 figures, accepted by ApJ for April 20, 2000, added acknowledgmen

Sds22, a PP1 phosphatase regulatory subunit, regulates epithelial cell polarity and shape [Sds22 in epithelial morphology]

<p>Abstract</p> <p>Background</p> <p>How epithelial cells adopt their particular polarised forms is poorly understood. In a screen for genes regulating epithelial morphology in <it>Drosophila</it>, we identified <it>sds22</it>, a conserved gene previously characterised in yeast.</p> <p>Results</p> <p>In the columnar epithelia of imaginal discs or follicle cells, mutation of <it>sds22 </it>causes contraction of cells along their apical-basal axis, resulting in a more cuboidal morphology. In addition, the mutant cells can also display altered cell polarity, forming multiple layers in follicle cells and leaving the epithelium in imaginal discs. In yeast, <it>sds22 </it>encodes a PP1 phosphatase regulatory subunit. Consistent with this, we show that <it>Drosophila </it>Sds22 binds to all four <it>Drosophila </it>PP1s and shares an overlapping phenotype with <it>PP1beta9c</it>. We also show that two previously postulated PP1 targets, Spaghetti Squash and Moesin are hyper-phosphorylated in <it>sds22 </it>mutants. This function is shared by the human homologue of Sds22, PPP1R7.</p> <p>Conclusion</p> <p>Sds22 is a conserved PP1 phosphatase regulatory subunit that controls cell shape and polarity.</p

Differential effects of two-pore channel protein 1 and 2 silencing in MDA-MB-468 breast cancer cells

Two-pore channel proteins, TPC1 and TPC2, are calcium permeable ion channels found localized to the membranes of endolysosomal calcium stores. There is increasing interest in the role of TPC-mediated intracellular signaling in various pathologies; however their role in breast cancer has not been extensively evaluated. TPC1 and TPC2 mRNA was present in all non-tumorigenic and tumorigenic breast cell lines assessed. Silencing of TPC2 but not TPC1 attenuated epidermal growth factor-induced vimentin expression in MDA-MB-468 breast cancer cells. This effect was not due to a general inhibition of epithelial to mesenchymal transition (EMT) as TPC2 silencing had no effect on epidermal growth factor (EGF)-induced changes on E-cadherin expression. TPC1 and TPC2 were also shown to differentially regulate cyclopiazonic acid (CPA)-mediated changes in cytosolic free Ca. These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells

Interoperability and FAIRness through a novel combination of Web technologies

Data in the life sciences are extremely diverse and are stored in a broad spectrum of repositories ranging from those designed for particular data types (such as KEGG for pathway data or UniProt for protein data) to those that are general-purpose (such as FigShare, Zenodo, Dataverse or EUDAT). These data have widely different levels of sensitivity and security considerations. For example, clinical observations about genetic mutations in patients are highly sensitive, while observations of species diversity are generally not. The lack of uniformity in data models from one repository to another, and in the richness and availability of metadata descriptions, makes integration and analysis of these data a manual, time-consuming task with no scalability. Here we explore a set of resource-oriented Web design patterns for data discovery, accessibility, transformation, and integration that can be implemented by any general- or special-purpose repository as a means to assist users in finding and reusing their data holdings. We show that by using off-the-shelf technologies, interoperability can be achieved atthe level of an individual spreadsheet cell. We note that the behaviours of this architecture compare favourably to the desiderata defined by the FAIR Data Principles, and can therefore represent an exemplar implementation of those principles. The proposed interoperability design patterns may be used to improve discovery and integration of both new and legacy data, maximizing the utility of all scholarly outputs

Microstructure, Elastic and Inelastic Properties of Partially Graphitized Biomorphic Carbons

The microstructural characteristics and amplitude dependences of the Young’s modulus E and internal friction (logarithmic decrement δ) of biocarbon matrices prepared by beech wood carbonization at temperatures Tcarb = 850–1600°C in the presence of a nickelcontaining catalyst have been studied. Using Xray diffraction and electron microscopy, it has been shown that the use of a nickel catalyst during carbon ization results in a partial graphitization of biocarbons at Tcarb ≥ 1000°C: the graphite phase is formed as 50 to 100nm globules at Tcarb = 1000°C and as 0.5 to 3.0μm globules at Tcarb = 1600°C. It has been found that the measured dependences E(Tcarb) and δ(Tcarb) contain three characteristic ranges of variations in the Young’s modulus and logarithmic decrement with a change in the carbonization temperature: E increases and δ decreases in the ranges Tcarb 1300°C; in the range 1000 < Tcarb < 1300°C, E sharply decreases and δ increases. The observed behavior of E(Tcarb) and δ(Tcarb) for biocarbons carbonized in the presence of nickel correlates with the evolution of their microstructure. The largest values of E are obtained for samples with Tcarb = 1000 and 1600°C. However, the samples with Tcarb = 1600°C exhibit a higher suscep tibility to microplasticity due to the presence of a globular graphite phase that is significantly larger in size and total volume.Peer reviewe

Low leakage-current InAsSb nanowire photodetectors on silicon

Axially doped p–i–n InAs0.93Sb0.07 nanowire arrays have been grown on Si substrates and fabricated into photodetectors for shortwave infrared detection. The devices exhibit a leakage current density around 2 mA/cm2 and a 20% cutoff of 2.3 μm at 300 K. This record low leakage current density for InAsSb based devices demonstrates the suitability of nanowires for the integration of III–V semiconductors with silicon technology

The Mass Distribution and Lifetime of Prestellar Cores in Perseus, Serpens, and Ophiuchus

We present an unbiased census of starless cores in Perseus, Serpens, and Ophiuchus, assembled by comparing large-scale Bolocam 1.1 mm continuum emission maps with Spitzer c2d surveys. We use the c2d catalogs to separate 108 starless from 92 protostellar cores in the 1.1 mm core samples from Enoch et al. (2006), Young et al. (2006), and Enoch et al. (2007). A comparison of these populations reveals the initial conditions of the starless cores. Starless cores in Perseus have similar masses but larger sizes and lower densities on average than protostellar cores, with sizes that suggest density profiles substantially flatter than r^-2. By contrast, starless cores in Serpens are compact and have lower masses than protostellar cores; future star formation will likely result in lower mass objects than the currently forming protostars. Comparison to dynamical masses estimated from the NH_3 survey of Perseus cores by Rosolowsky et al. (2007) suggests that most of the starless cores are likely to be gravitationally bound, and thus prestellar. The combined prestellar core mass distribution includes 108 cores and has a slope of -2.3+/-0.4 for M>0.8 Msun. This slope is consistent with recent measurements of the stellar initial mass function, providing further evidence that stellar masses are directly linked to the core formation process. We place a lower limit on the core-to-star efficiency of 25%. There are approximately equal numbers of prestellar and protostellar cores in each cloud, thus the dense prestellar core lifetime must be similar to the lifetime of embedded protostars, or 4.5x10^5 years, with a total uncertainty of a factor of two. Such a short lifetime suggests a dynamic, rather than quasi-static, core evolution scenario, at least at the relatively high mean densities (n>2x10^4 cm^-3) to which we are sensitive.Comment: 27 pages, 15 figures, 5 tables, accepted for publication in ApJ. Version with full resolution figures available at http://www.astro.caltech.edu/~menoch/corespaper