O-GlcNAc – a posttranslational modification implicated in Alzheimer disease?

O-linked N-acetylglucosamine (O-GlcNAc) is a highly dynamic posttranslational modification which has been found on a myriad of nucleocytoplasmic proteins. O-GlcNAc addition and removal are catalyzed by two conserved enzymes, O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (OGA). Alzheimer disease (AD) is one of the most common forms of dementia. The histopathological hallmarks of AD brain include neurofibrillary tangles of hyperphosphorylated tau and senile plaques consisting mainly of aggregated amyloid β-peptides which are generated from a larger transmembrane protein, the amyloid precursor protein (APP). O-GlcNAc has been extensively studied in the context of AD. However, contradicting results have demonstrated either increased or decreased O-GlcNAcylation in AD brain. To date the underlying cause(s) as well as potential consequences of altered O-GlcNAcylation in AD are unknown. Both the microtubule-associated protein tau and APP are O-GlcNAc-modified. While some studies show that increased O-GlcNAcylation reduces tau hyperphosphorylation, the function of the O-GlcNAc modification of APP is not yet understood. In this work, the potential involvement of O-GlcNAc in different aspects of AD pathology was investigated. For this purpose, a recently established in vitro OGT assay was used to demonstrate the O-GlcNAcylation of cyclin-dependent kinase 5 (cdk5), a kinase that phosphorylates both APP and tau and has been implicated in AD pathogenesis. The functional role of O-GlcNAcylation of cdk5 remains to be elucidated. Since OGT assays are useful tools for the analysis of OGT activity or for the identification of novel OGT targets, the established in vitro OGT assay was further refined using the nuclear pore protein Nup62 as a model substrate. To investigate the (potential) role of APP´s O-GlcNAcylation, effects of O-GlcNAc modulation on the proteolytic processing of APP were analyzed in cell culture studies. Increased O-GlcNAc expression by OGA inhibition did, however, not alter levels of the APP cleavage products sAPPα and sAPPβ. Furthermore, O-GlcNAc and, for the first time, O-GlcNAc cycling enzymes were investigated in brain samples of subjects with AD and amnestic mild cognitive impairment (MCI), a prodromal stage of AD. In AD brains, increased O-GlcNAcylation correlated with reduced OGA expression and activity while OGT expression was unaltered when compared with age-matched controls. In MCI brains, no changes in O-GlcNAc, OGA or OGT expression were observed. Taken together this work suggests that O-GlcNAc may not play a direct role in APP processing and that altered O-GlcNAcylation may be a late event in the progression of AD. In combination with recent reports demonstrating positive effects of OGA inhibition in animal models of AD, it is obvious that further studies are needed to elucidate the role of O-GlcNAc in AD

Nutritional diversity in leaves of various amaranth (Amaranthus spp.) genotypes and its resilience to drought stress

The nutritional diversity in leaves of twelve accessions of four amaranth species (Amaranthus caudatus, A. cruentus, A. hybridus, A. hypochondriacus) was studied in a randomized complete block design (n = 5). The accessions revealed high contents of the macronutrients K, Ca, Mg, and P, while the micronutrients Fe and Zn were comparatively low (542 – 717, 304 – 497, 131 – 230, 74 – 166, 0.9 – 1.3, 0.4 – 0.9 mg 100 g-1 fresh weight, respectively). Protein contents were found to be higher (23 – 32%) compared to other commonly consumed leafy vegetables in Sub-Saharan-Africa. Phenolic acid and flavonoid contents strongly varied between accessions and to some extent were lower in comparison to those reported in literature. Amaranth is reported to be drought tolerant, thus, one accession of each species was subjected to two different drought stress conditions (moderate – 35 – 45% field capacity, severe – 15 – 25% field capacity, n = 3). Well-watered plants were used as control (60 – 70% field capacity). A significant reduction in plant height and fresh matter occurred in all accessions with increasing drought stress, whereas contents of nutritional compounds increased. Phenolic acids and flavonoid contents in all accessions/species were not affected by drought stress except for A. cruentus where total phenolic acids significantly increase

ZuS - Zukunftsstrategie Lehrer*innenbildung Köln (Teilprojekt Qualitätssicherung). Skalendokumentation zum Fragebogen des hochschulweiten Bildungsmonitorings, Messzeitpunkt 1, Teil A.

Die vorliegende Dokumentation ist Teil eines Bildungsmonitorings, das im Rahmen des an der Universität zu Köln durchgeführten Projekts „Zukunftsstrategie Lehrer*innenbildung Köln – Heterogenität und Inklusion gestalten“ (ZuS) im Teilprojekt Qualitätssicherung (QS) während des Sommersemesters 2016 durchgeführt wurde. Das Bildungsmonitoring soll auf einer Makroebene Einblick geben in Prozesse des Kompetenzerwerbs während des Lehramtsstudiums und dazu beitragen, Merkmale der Ausbildung zu erkennen, die dabei von Bedeutung sind. Drei wesentliche Maßnahmen werden im Bildungsmonitoring ergriffen: Die Erfassung der Kompetenzentwicklung von Lehramtsstudierenden, die angebotenen und genutzten Lerngelegenheiten als Bedingungen der Kompetenzentwicklung und die Prüfung des Einflusses der Lerngelegenheiten auf die Kompetenzentwicklung. Verwendet wird ein Mehr-Kohorten-Längsschnitt-Design. Primäre Zielgruppe sind Bachelor- und Masterstudierende, die sich im Sommersemester 2016 im zweiten Fachsemester befanden. Geplant ist, diese beiden Kohorten über die kommenden zwei Jahren (2017, 2018) wissenschaftlich zu begleiten, um während der Projektlaufzeit ein umfassendes Bild über den Kompetenzerwerb während der gesamten Lehramtsausbildung an der Universität zu Köln zu erhalten. Die hier abgebildete Skalendokumentation umfasst den allgemeinen Teil des Bildungsmonitorings 2016. Sie informiert über die verwendeten Variablen, Items und Skalen, die bei der Befragung der Studierenden eingesetzt wurden. Zusätzlich werden technische Variablen berichtet, die bei der Datenerhebung und -aufbereitung relevant waren

Continuous Phosphorus Recovery by Heterogeneous Nucleation: Challenges in Solid-Liquid Separation

Phosphorous (P) is an essential natural resource of limited availability. Furthermore, many countries, including Germany, have no access to P sources and are entirely dependent on P imports to cover their demand. Therefore the recovery of P is a topic of distinct importance. In the past decades a manifold of processes for P recovery from wastewater have been developed. The P-RoC-process (Phosphorus Recovery by Crystallization) is a technique developed by Competence Center for Material Moisture (CMM), KIT, based on crystallization of P on a Calcium-Silicate-Hydrate (CSH) substrate [1]. The feasibility of the approach has been shown on the lab scale and also as a semi-batch process on the pilot scale in a side stream of a municipal sewage plant. For full implementation of the process, a transition from semi-batch to a continuous process is desirable. However a crucial question still to be solved is the removal of the P-loaded substrate from the process. Challenges for the CSH separation are the particle size distribution that will result in a distribution in reaction kinetics and thus a difference in P coverage with particle size. Additionally comminution of the highly porous particles might also be an issue. The task at hand thus requires a separation unit that allows for classification as well as for separation of the particles. In this paper we present how the continuous classification and separation of P-loaded CSH is solved by using a hydrocyclone. For this cause an experimental setup was developed in order to realize the continuous P crystallization on CSH substrate and removal of CSH on the pilot scale

Abeta, oxidative stress in Alzheimer disease: Evidence based on proteomics studies

AbstractThe initiation and progression of Alzheimer disease (AD) is a complex process not yet fully understood. While many hypotheses have been provided as to the cause of the disease, the exact mechanisms remain elusive and difficult to verify. Proteomic applications in disease models of AD have provided valuable insights into the molecular basis of this disorder, demonstrating that on a protein level, disease progression impacts numerous cellular processes such as energy production, cellular structure, signal transduction, synaptic function, mitochondrial function, cell cycle progression, and proteasome function. Each of these cellular functions contributes to the overall health of the cell, and the dysregulation of one or more could contribute to the pathology and clinical presentation in AD. In this review, foci reside primarily on the amyloid β-peptide (Aβ) induced oxidative stress hypothesis and the proteomic studies that have been conducted by our laboratory and others that contribute to the overall understanding of this devastating neurodegenerative disease. This article is part of a Special Issue entitled: Misfolded Proteins, Mitochondrial Dysfunction, and Neurodegenerative Diseases

Modulation of the Tumor-Associated Immuno-Environment by Non-Invasive Physical Plasma

Over the past 15 years, investigating the efficacy of non-invasive physical plasma (NIPP) in cancer treatment as a safe oxidative stress inducer has become an active area of research. So far, most studies focused on the NIPP-induced apoptotic death of tumor cells. However, whether NIPP plays a role in the anti-tumor immune responses need to be deciphered in detail. In this review, we summarized the current knowledge of the potential effects of NIPP on immune cells, tumor–immune interactions, and the immunosuppressive tumor microenvironment. In general, relying on their inherent anti-oxidative defense systems, immune cells show a more resistant character than cancer cells in the NIPP-induced apoptosis, which is an important reason why NIPP is considered promising in cancer management. Moreover, NIPP treatment induces immunogenic cell death of cancer cells, leading to maturation of dendritic cells and activation of cytotoxic CD8+ T cells to further eliminate the cancer cells. Some studies also suggest that NIPP treatment may promote anti-tumor immune responses via other mechanisms such as inhibiting tumor angiogenesis and the desmoplasia of tumor stroma. Though more evidence is required, we expect a bright future for applying NIPP in clinical cancer management

An HST/WFC3-IR Morphological Survey of Galaxies at z = 1.5-3.6: II. The Relation between Morphology and Gas-Phase Kinematics

We analyze rest-frame optical morphologies and gas-phase kinematics as traced by rest-frame far-UV and optical spectra for a sample of 204 star forming galaxies in the redshift range z ~ 2-3 drawn from the Keck Baryonic Structure Survey (KBSS). We find that spectroscopic properties and gas-phase kinematics are closely linked to morphology: compact galaxies with semi-major axis radii r <~ 2 kpc are substantially more likely than their larger counterparts to exhibit LyA in emission. Although LyA emission strength varies widely within galaxies of a given morphological type, all but one of 19 galaxies with LyA equivalent width W_LyA > 20 Angstroms have compact and/or multiple-component morphologies with r <= 2.5 kpc. The velocity structure of absorption lines in the galactic continuum spectra also varies as a function of morphology. Galaxies of all morphological types drive similarly strong outflows (as traced by the blue wing of interstellar absorption line features), but the outflows of larger galaxies are less highly ionized and exhibit larger optical depth at the systemic redshift that may correspond to a decreasing efficiency of feedback in evacuating gas from the galaxy. This v ~ 0 km/s gas is responsible both for shifting the mean absorption line redshift and attenuating W_LyA (via a longer resonant scattering path) in galaxies with larger rest-optical half light radii. In contrast to galaxies at lower redshifts, there is no evidence for a correlation between outflow velocity and inclination, suggesting that outflows from these puffy and irregular systems may be poorly collimated. (Abbrev.)Comment: 18 pages, 11 figures. Revised version accepted for publication in ApJ. Version with full-resolution figures is available at http://di.utoronto.ca/~drlaw/Papers/wfc3_uvspec.pd

Proteomics Identifies Substrates and a Novel Component in hSnd2-Dependent ER Protein Targeting

Importing proteins into the endoplasmic reticulum (ER) is essential for about 30% of the human proteome. It involves the targeting of precursor proteins to the ER and their insertion into or translocation across the ER membrane. Furthermore, it relies on signals in the precursor polypeptides and components, which read the signals and facilitate their targeting to a protein-conducting channel in the ER membrane, the Sec61 complex. Compared to the SRP- and TRC-dependent pathways, little is known about the SRP-independent/SND pathway. Our aim was to identify additional components and characterize the client spectrum of the human SND pathway. The established strategy of combining the depletion of the central hSnd2 component from HeLa cells with proteomic and differential protein abundance analysis was used. The SRP and TRC targeting pathways were analyzed in comparison. TMEM109 was characterized as hSnd3. Unlike SRP but similar to TRC, the SND clients are predominantly membrane proteins with N-terminal, central, or C-terminal targeting signals

The SINS/zC-SINF survey of z~2 galaxy kinematics: Outflow properties

Based on SINFONI Ha, [NII] and [SII] AO data of 30 z \sim 2 star-forming galaxies (SFGs) from the SINS and zcSINF surveys, we find a strong correlation of the Ha broad flux fraction with the star formation surface density of the galaxy, with an apparent threshold for strong outflows occurring at 1 Msun yr^-1 kpc^-2. Above this threshold, we find that SFGs with logm_\ast>10 have similar or perhaps greater wind mass loading factors (eta = Mdotout/SFR) and faster outflow velocities than lower mass SFGs. This trend suggests that the majority of outflowing gas at z \sim 2 may derive from high-mass SFGs, and that the z \sim 2 mass-metallicity relation is driven more by dilution of enriched gas in the galaxy gas reservoir than by the efficiency of outflows. The mass loading factor is also correlated with the SFR and inclination, such that more star-forming and face-on galaxies launch more powerful outflows. For galaxies that have evidence for strong outflows, we find that the broad emission is spatially extended to at least the half-light radius (\sim a few kpc). We propose that the observed threshold for strong outflows and the observed mass loading of these winds can be explained by a simple model wherein break-out of winds is governed by pressure balance in the disk. Using the ratio of the [SII] doublet in a broad and narrow component, we find that outflowing gas has a density of \sim10-100 cm^-3, significantly less than that of the star forming gas (600 cm^-3).Comment: 7 pages, 3 figures, accepted by Ap

Proteomics Identifies Substrates and a Novel Component in hSnd2-Dependent ER Protein Targeting

Importing proteins into the endoplasmic reticulum (ER) is essential for about 30% of the human proteome. It involves the targeting of precursor proteins to the ER and their insertion into or translocation across the ER membrane. Furthermore, it relies on signals in the precursor polypeptides and components, which read the signals and facilitate their targeting to a protein-conducting channel in the ER membrane, the Sec61 complex. Compared to the SRP- and TRC-dependent pathways, little is known about the SRP-independent/SND pathway. Our aim was to identify additional components and characterize the client spectrum of the human SND pathway. The established strategy of combining the depletion of the central hSnd2 component from HeLa cells with proteomic and differential protein abundance analysis was used. The SRP and TRC targeting pathways were analyzed in comparison. TMEM109 was characterized as hSnd3. Unlike SRP but similar to TRC, the SND clients are predominantly membrane proteins with N-terminal, central, or C-terminal targeting signals