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  • 1
    Publication Date: 2019
    Description: The molecular mechanisms underlying bipolar disorder (BPD) have remained largely unknown. Postmortem brain tissue studies comparing BPD patients with healthy controls have produced a heterogeneous array of potentially implicated protein-coding RNAs. We hypothesized that dysregulation of not only coding, but multiple classes of RNA (coding RNA, long non-coding (lnc) RNA, circular (circ) RNA, and/or alternative splicing) underlie the pathogenesis of BPD. Using non-polyadenylated libraries we performed RNA sequencing in postmortem human medial frontal gyrus tissue from BPD patients and healthy controls. Twenty genes, some of which not previously implicated in BPD, were differentially expressed (DE). PCR validation and replication confirmed the implication of these DE genes. Functional in silico analyses identified enrichment of angiogenesis, vascular system development and histone H3-K4 demethylation. In addition, ten lncRNA transcripts were differentially expressed. Furthermore, an overall increased number of alternative splicing events in BPD was detected, as well as an increase in the number of genes carrying alternative splicing events. Finally, a large reservoir of circRNAs populating brain tissue not affected by BPD is described, while in BPD altered levels of two circular transcripts, cNEBL and cEPHA3, are reported. cEPHA3, hitherto unlinked to BPD, is implicated in developmental processes in the central nervous system. Although we did not perform replication analyses of non-coding RNA findings, our findings hint that RNA dysregulation in BPD is not limited to coding regions, opening avenues for future pharmacological investigations and biomarker research.
    Electronic ISSN: 2073-4425
    Topics: Biology
    Published by MDPI
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  • 2
    Publication Date: 2019-11-19
    Description: The molecular mechanisms underlying bipolar disorder (BPD) have remained largely unknown. Postmortem brain tissue studies comparing BPD patients with healthy controls have produced a heterogeneous array of potentially implicated protein-coding RNAs. We hypothesized that dysregulation of not only coding, but multiple classes of RNA (coding RNA, long non-coding (lnc) RNA, circular (circ) RNA, and/or alternative splicing) underlie the pathogenesis of BPD. Using non-polyadenylated libraries we performed RNA sequencing in postmortem human medial frontal gyrus tissue from BPD patients and healthy controls. Twenty genes, some of which not previously implicated in BPD, were differentially expressed (DE). PCR validation and replication confirmed the implication of these DE genes. Functional in silico analyses identified enrichment of angiogenesis, vascular system development and histone H3-K4 demethylation. In addition, ten lncRNA transcripts were differentially expressed. Furthermore, an overall increased number of alternative splicing events in BPD was detected, as well as an increase in the number of genes carrying alternative splicing events. Finally, a large reservoir of circRNAs populating brain tissue not affected by BPD is described, while in BPD altered levels of two circular transcripts, cNEBL and cEPHA3, are reported. cEPHA3, hitherto unlinked to BPD, is implicated in developmental processes in the central nervous system. Although we did not perform replication analyses of non-coding RNA findings, our findings hint that RNA dysregulation in BPD is not limited to coding regions, opening avenues for future pharmacological investigations and biomarker research.
    Electronic ISSN: 2073-4425
    Topics: Biology
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  • 3
  • 4
    Publication Date: 2014-02-11
    Description: Post-transcriptional regulation of RNA stability and localization underlies a wide array of developmental processes, such as axon guidance and epithelial morphogenesis. In Drosophila , ectopic expression of the classically Golgi peripheral protein dGRASP at the plasma membrane is achieved through its mRNA targeting at key developmental time-points, in a process critical to follicular epithelium integrity. However, the trans -acting factors that tightly regulate the spatio-temporal dynamics of dgrasp are unknown. Using an in silico approach, we identified two putative HOW Response Elements (HRE1 and HRE2) within the dgrasp open reading frame for binding to Held Out Wings (HOW), a member of the S ignal T ransduction and A ctivation of R NA family of RNA-binding proteins. Using RNA immunoprecipitations, we confirmed this by showing that the short cytoplasmic isoform of HOW binds directly to dgrasp HRE1. Furthermore, HOW loss of function in vivo leads to a significant decrease in dgrasp mRNA levels. We demonstrate that HRE1 protects dgrasp mRNA from cytoplasmic degradation, but does not mediate its targeting. We propose that this binding event promotes the formation of ribonucleoprotein particles that ensure dgrasp stability during transport to the basal plasma membrane, thus enabling the local translation of dgrasp for its roles at non-Golgi locations.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 5
    ISSN: 1573-6822
    Keywords: cytotoxicity ; nitrogen mustard ; respiratory epithelium in culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Mechlorethamine (HN2) is an alkylating agent usually used in cancer chemotherapy. Nevertheless, HN2 is extremely toxic and its use is accompanied by severe side-effects that may cause lung complications. Many studies report the morphological and biochemical modifications induced by sulfur mustard (SM) but no report has been published concerning the toxic effects of HN2 on the ultrastructural and functional activity of surface respiratory epithelial cells. This study was performed on rabbit tracheal epithelium (RTE) cells in primary culture. The functional activity of the culture was evaluated by measuring the ciliary beating frequency (CBF) of the ciliated cells using a videomicroscopic method, and the culture growth was determined by an image analysis system. The morphological aspects of the cells were analyzed by light, scanning electron, and transmission electron microscopy. An important inhibition of cell growth was observed associated with a detachment of the outgrowth cells. Morphological changes were expressed by vacuolization, increases in the intercellular spaces, and by disorganization of the cytoskeleton associated with a specific attack of the ciliated cells that show ciliary blebbing. The sudden CBF inhibition is more likely due to the detachment and the death of the ciliated cells than to a specific ciliotoxic effect of HN2. All these observations demonstrated the high sensitivity of respiratory epithelial cells to HN2 and showed that HN2-induced injuries were irreversible, and time- and dose-dependent.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-7357
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A procedure of optimization of Si-implanted thermistors was started, with the final aim to develop bolometers with a resolution of a few eV in the keV range. The initial approach was to assume that a thermal decoupling between phonons and hopping electrons establishes inside the thermistors, with consequent reduction of the sensitivity and incomplete transfer of the particle generated phonons to the conduction electrons. This assumption however failed in explaining the collected experimental data, which can be described much more satisfactorily introducing an electric field dependance of the thermistor resistance. This alternative interpretation modifies the parameter choice for an optimum device
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1352-8661
    Keywords: vitreous body ; 23na nuclear magnetic resonance ; 23na relaxation times
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics
    Notes: Abstract We have studied the nuclear magnetic resonance (NMR) relaxation behavior, and thus the dynamic properties, of the sodium ion in the vitreous body at different temperatures. The23Na NMR spectrum exhibits a resonance, the intensity of which accounts for an ion visibility of 100%. The23Na longitudinal and transverse relaxation times, at all temperatures but the highest, present two components, suggesting that the sodium ions are present in two states of different mobility, whose populations are in slow exchange on the NMR time scale. The correlation times and quadrupole coupling constants for the two sodium pools have been derived. The faster relaxation of a fraction of the vitreal sodium has tentatively been ascribed to the influence of the macromolecular framework of the vitreous body. The reported information may be of use for the understanding of the diagnostic applications of23Na magnetic resonance imaging of the ocular structures.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-8345
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The experimental study of the frequency response of burning solid propellants has been done using, as external forcing energy source, a CO2 laser (60 W, 10.6 μm). The laser radiant flux intensity was sinusoidally modulated and the response of the burning propellant was detected by measuring the recoil force generated by the gases coming out from the burning surface using a strain-gauge load cell which can operate inside the combustion chamber at the operating pressure. The tests were performed in the subatmospheric pressure range, and a composite propellant (AP.HTPB/86.14) was used. The combustion chamber was filled by inert gas (N2), and for each working pressure several tests were carried out at different radiant flux frequency modulations in the range from 5 to 50 Hz. The results evince that the recoil force amplitude depends on the forcing laser frequency with a maximum for every working pressure. This experimental data set was then used to compare the nonlinear frequency response curves obtained by numerical integration of the combustion model equations. Comparisons between experimental and numerical results at 0.3 and 0.5 atm are shown, and the general trend, obtained by numerical simulations, of the propellant frequency response vs pressure in a broader range is presented and discussed.
    Type of Medium: Electronic Resource
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  • 9
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    Beverly Hills, Calif. : Periodicals Archive Online (PAO)
    Environment and behavior. 19:2 (1987:Mar.) 150 
    ISSN: 0013-9165
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Psychology
    Notes: HOME INTERIORS: A EUROPEAN PERSPECTIVE
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  • 10
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    Beverly Hills, Calif. : Periodicals Archive Online (PAO)
    Environment and behavior. 19:2 (1987:Mar.) 180 
    ISSN: 0013-9165
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Psychology
    Notes: HOME INTERIORS: A EUROPEAN PERSPECTIVE
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