202,711 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Drosophila REEP1 modulates ER morphology and ER stress
No full textDefects in endoplasmic reticulum (ER) membrane shaping and in lipid metabolism seem to be crucial mechanisms underlying Hereditary Spastic Paraplegia (HSP), a complex genetic disorder characterized by the axonal degeneration of corticospinal tracts. Here we report the analysis of a Drosophila melanogaster model of SPG31, an autosomal dominant form of HSP caused by mutations in the Receptor Expression Enhancing Protein1 gene (REEP1). REEP1 coordinates ER shaping within the tubular ER and confers resistance to ER stress in neurons, but the mechanism of this effect remains to be elucidated. In this work, we analyzed the effects of loss of D-REEP1 (REEPA) on the ER morphology, the Unfolded Protein Response (UPR), the locomotor activity and longevity. The absence of REEPA negatively affected longevity reducing lifespan as well as the locomotor activity. Moreover, REEPA mutant presented a larger proportion of apparent ER sheets, the up-regulation of ER-stress sensor Bip, the activation of Ire1 and ATF6 pathways, and a drastic reduction of the transcription level of two major enzymes involved in LDs biogenesis. The administration to REEPA mutant of naringenin, a flavanone known for its neuroprotective effects, rescued lifespan defect and ER homeostasis by decreasing UPR activation and enhancing LDs biogenesis, thus representing a promising strategy for the management of HSP symptoms
Carbohydrate- and conformation-dependent cargo capture for ER-exit
No full textSome secretory proteins leave the endoplasmic reticulum (ER) by a receptor-mediated cargo capture mechanism, but the signals required for the cargo-receptor interaction are largely unknown. Here, we describe a novel targeting motif that is composed of a high-mannose type oligosaccharide intimately associated with a surface-exposed peptide beta-hairpin loop. The motif accounts for lectin ERGIC-53-assisted ER-export of the lyososomal enzyme procathepsin Z. The second oligosaccharide chain of procathepsin Z exhibits no binding activity for ERGIC-53, illustrating the selective lectin properties of ERGIC-53. Our data suggest that the conformation-based motif is only present in fully folded procathepsin Z and that its recognition by ERGIC-53 reflects a quality control mechanism that acts complementary to the primary folding machinery in the ER. A similar oligosaccharide/beta-hairpin loop structure is present in cathepsin C, another cargo of ERGIC-53, suggesting the general nature of this ER-exit signal. To our knowledge this is the first documentation of an ER-exit signal in soluble cargo in conjunction with its decoding by a transport receptor
The isolated ER-Golgi intermediate compartment exhibits properties that are different from ER and cis-Golgi
No full textA procedure has been established in Vero cells for the isolation of an intermediate compartment involved in protein transport from the ER to the Golgi apparatus. The two-step subcellular fractionation procedure consists of Percoll followed by Metrizamide gradient centrifugation. Using the previously characterized p53 as a marker protein, the average enrichment factor of the intermediate compartment was 41. The purified fraction displayed a unique polypeptide pattern. It was largely separated from the rough ER proteins ribophorin I, ribophorin II, BIP, and protein disulfide isomerase, as well as from the putative cis-Golgi marker N-acetylglucosamine-1-phosphodiester-alpha-N-acetylglucosaminidase, the second of the two enzymes generating the lysosomal targeting signal mannose-6-phosphate. The first enzyme, N-acetylglucosaminylphosphotransferase, for which previous biochemical evidence had suggested both a pre- and a cis-Golgi localization in other cell types, cofractionated with the cis-Golgi rather than the intermediate compartment in Vero cells. The results suggest that the intermediate compartment defined by p53 has unique properties and does not exhibit typical features of rough ER and cis-Golgi
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
The involvement of ER calcium in abiotic stress tolerance
No full textCalcium application is known to reduce the deleterious effects of NaCl in many plant species. Ca2+ supplementation is thought to act by inhibiting ion channels that allow Na+ influx and by blocking Na+-induced K+ efflux. I generated transgenic Arabidopsis lines that constitutively express a low affinity, high capacity Calcium Binding Peptide (CBP) localized to the endoplasmic reticulum. Four independent transformed lines, two that also contained GFP and two that lacked it, were analyzed and contained up to 10% more total calcium than GFP control and wild-type plants. Each of these lines also showed increased K+ that was balanced by a decrease in Na+ accumulation. There were no significant changes in the relative amounts of other ions.
ER-CBP transgenic plants exhibited better salt and osmotic tolerance, increased survival in soil under intermittent drought conditions, longer root growth, higher chlorophyll content, and higher total seed production compared to GFP transgenic plants and control plants. One member of the CIPK (CBL-Interacting Protein Kinase) family, CIPK6, showed higher transcript levels in ER-CBP lines along with other drought-associated genes such as
DREB1a and rd29a, even under non-stress conditions. However, DREB2a transcript level was not affected by ER-CBP.
CIPK6 interacts with a Calcineurin B-Like Protein(s) (CBL) and was recently shown to interact with the C-terminus of the Arabidopsis Potassium Transporter1 (AKT1) protein. Using cipk6 null mutants, I showed that expression of both ER-CBP and CIPK6 was needed to achieve salt tolerance.
I used two methods, confocal ratio imaging of Indo-1 and cytoplasmically-expressed aequorin luminescence, to detect transient changes in [Ca2+]cyt in response to a salt stimulus.
There were no significant differences in [Ca2+]cyt measured by confocal ratio imaging between ER-CBP transgenic plants and control Arabidopsis plants in response to a short term salt treatment ( ~ 20 min). However, after three days incubation on 100 mM NaCl, ER-CBP lines had a higher steady state level of [Ca2+]cyt than wild type plants. Similarly, ER-CBP transgenic plants expressing aequorin in the cytoplasm did not show significant differences in Ca2+ spikes in response to 150 mM or 300 mM NaCl. After seedlings were grown on Ca2+ depleted media for 5 days, ER-CBP transgenic plants maintained Ca2+ peak heights similar to that seen before the low-calcium treatment, but control plants showed a decrease in Ca2+ spikes. This suggests that ER-CBP transgenic lines utilized extra ER Ca2+ stores under continual stress to maintain optimal Ca2+ levels in the cytoplasm.
Trehalose has been shown to play an important role in drought tolerance. It is one of the most studied osmoprotectants. ER-CBP transgenic lines exhibited increased Trehalose 6-phosphate synthase (TPS) and Trehalose-6-phosphate phosphatase (TPP) expression. Accordingly, the trehalose content of ER-CBP lines was significantly higher compared to control plants. These results strongly implicate ER calcium as being critical for sustained tolerance to drought and salt in Arabidopsis
Gedragsinzichten bieden meer beleidskansen dan er nu worden benut
No full textGedragsinzichten zijn onontbeerlijk om te komen tot effectief beleid, de mens is immers geen homo economicus. Dat geldt echter niet alleen voor uitvoeringsvraagstukken, maar ook voor het ontwerpen van beleid. Hier ligt er nog een groot onbenut potentieel.Policy Analysi
Targeting of protein ERGIC-53 to the ER/ERGIC/cis-Golgi recycling pathway
No full textERGIC-53 is a lectin-type membrane protein that continuously recycles between the ER, ER-Golgi intermediate compartment (ERGIC) and the cis-Golgi. To identify the targeting signals that mediate this recycling, N-glycosylated and myc-tagged variants of ERGIC-53 were constructed. By monitoring endoglycosidase H resistance, we measured the loss from the ER-ERGIC-cis-Golgi cycle of ERGIC-53. A domain exchange approach with the plasma membrane reporter protein CD4 showed that the transmembrane and the lumenal domains are not sufficient, while the cytoplasmic domain of ERGIC-53 is required and sufficient for pre-medial-Golgi localization. However, the ERGIC-53 cytoplasmic domain on CD4 lead to increased ER-staining by immunofluorescence microscopy indicating that this domain alone cannot provide for unbiased recycling through the ER-ERGIC-cis-Golgi compartments. Complete progress through the ER-ERGIC-cis-Golgi recycling pathway requires the cytoplasmic domain acting together with the lumenal domain of ERGIC-53. Dissection of the cytoplasmic domain revealed a COOH-terminal di-lysine ER-retrieval signal, KKFF, and an RSQQE targeting determinant adjacent to the transmembrane domain. Surprisingly, the two COOH-terminal phenylalanines influence the targeting. They reduce the ER-retrieval capacity of the di-lysine signal and modulate the RSQQE determinant
Fahrettin er-Razi’nin Tartışmaları - I
No full textEfendimiz ve hocamız, Allah’a davet eden, dinin gururu olan Ebû Abdullah
Muhammed b. Ömer b. Hüseyin er-Râzî (r.a) dedi ki: Hamd âlemlerin rabbi olan
Allah’a, salât Hz. Muhammed ve onun bütün Ehl-i Beyt’ine olsun. Maveraünnehir bölgesine girdiğimde önce Buhârâ’ya sonra Semerkant’a gittim. Daha sonra
oradan Hocend’e, sonra Benâkit denilen yere, sonra Gazne’ye ve Hint bölgesine
geçtim. Bu yerlerin her birinde oranın seçkinleri ve önde gelenleriyle tartışmalar
ve münakaşalarım oldu
Eeyarestatin 1 interferes with both retrograde and anterograde intracellular trafficking pathways
No full textBackground: The small molecule Eeyarestatin I (ESI) inhibits the endoplasmic reticulum (ER)-cytosol dislocation and
subsequent degradation of ERAD (ER associated protein degradation) substrates. Toxins such as ricin and Shiga/Shiga-like
toxins (SLTx) are endocytosed and trafficked to the ER. Their catalytic subunits are thought to utilise ERAD-like mechanisms
to dislocate from the ER into the cytosol, where a proportion uncouples from the ERAD process, recovers a catalytic
conformation and destroys their cellular targets. We therefore investigated ESI as a potential inhibitor of toxin dislocation.
Methodology and Principal Findings: Using cytotoxicity measurements, we found no role for ESI as an inhibitor of toxin
dislocation from the ER, but instead found that for SLTx, ESI treatment of cells was protective by reducing the rate of toxin
delivery to the ER. Microscopy of the trafficking of labelled SLTx and its B chain (lacking the toxic A chain) showed a delay in
its accumulation at a peri-nuclear location, confirmed to be the Golgi by examination of SLTx B chain metabolically labelled
in the trans-Golgi cisternae. The drug also reduced the rate of endosomal trafficking of diphtheria toxin, which enters the
cytosol from acidified endosomes, and delayed the Golgi-specific glycan modifications and eventual plasma membrane
appearance of tsO45 VSV-G protein, a classical marker for anterograde trafficking.
Conclusions and Significance: ESI acts on one or more components that function during vesicular transport, whilst at least
one retrograde trafficking pathway, that of ricin, remains unperturbed
- …
