bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular insights into mechanisms of intramembrane proteolysis through signal peptide peptidase (SPP)
Authors: Schröder Bernd , Saftig Paul 
Published: April 2010

The processing of membrane-anchored signalling molecules and transcription factors by RIP (regulated intramembrane proteolysis) is a major signalling paradigm in eukaryotic cells. Intramembrane cleaving proteases liberate fragments from membrane-bound precursor proteins which typically fulfil functions such as cell signalling and regulation, immunosurveillance and intercellular communication. Furthermore, they are thought to be involved in the development and propagation of several diseases, such as Alzheimer's disease and hepatitis C virus infection. In this issue of the Biochemical Journal, Schrul and colleagues investigate the interaction of the endoplasmic reticulum-resident intramembrane cleaving SPP (signal peptide peptidase) with different type II oriented transmembrane proteins. A combination of co-immunoprecipitation experiments using wild-type and a dominant-negative SPP with electrophoretic protein separations under native conditions revealed selectivity of the interaction. Depending on the interacting protein, SPP formed complexes of different sizes. SPP could build tight interactions not only with signal peptides, but also with pre- and mis-folded proteins. Whereas signal peptides are direct substrates for SPP proteolysis, the study suggests that SPP may be involved in the controlled sequestration of possibly toxic membrane protein species in a proteolysis-independent manner. These large oligomeric membrane protein aggregates may then be degraded by the proteasome or autophagy.
Quantitative analysis of intact apolipoproteins in human HDL by top-down differential mass spectrometry
Authors: Mazur Matthew T. , Cardasis Helene L. , Spellman Daniel S. , Liaw Andy , Yates Nathan A. , Hendrickson Ronald C. 
Published: April 2010

Top-down mass spectrometry holds tremendous potential for the characterization and quantification of intact proteins, including individual protein isoforms and specific posttranslationally modified forms. This technique does not require antibody reagents and thus offers a rapid path for assay development with increased specificity based on the amino acid sequence. Top-down MS is efficient whereby intact protein mass measurement, purification by mass separation, dissociation, and measurement of product ions with ppm mass accuracy occurs on the seconds to minutes time scale. Moreover, as the analysis is based on the accurate measurement of an intact protein, top-down mass spectrometry opens a research paradigm to perform quantitative analysis of “unknown” proteins that differ in accurate mass. As a proof of concept, we have applied differential mass spectrometry (dMS) to the top-down analysis of apolipoproteins isolated from human HDL
3
. The protein species at 9415.45 Da demonstrates an average fold change of 4.7 (p-value 0.017) and was identified as an
O
-glycosylated form of apolipoprotein C-III [NANA-(2 → 3)-Gal-
β
(1 → 3)-GalNAc, +656.2037 Da], a protein associated with coronary artery disease. This work demonstrates the utility of top-down dMS for quantitative analysis of intact protein mixtures and holds potential for facilitating a better understanding of HDL biology and complex biological systems at the protein level.
EphrinBs/EphBs Signaling Is Involved in Modulation of Spinal Nociceptive Processing through a Mitogen-activated Protein Kinases-dependent Mechanism
Authors: Ruan Jia-Ping , Zhang Hong-Xing , Lu Xian-Fu , Liu Yue-Peng , Cao Jun-Li 
Published: April 2010

Background
Our previous studies have demonstrated that EphBs receptors and ephrinBs ligands were involved in modulation of spinal nociceptive information. However, the downstream mechanisms that control this process are not well understood. The aim of this study was to further investigate whether mitogen-activated protein kinases (MAPKs), as the downstream effectors, participate in modulation of spinal nociceptive information related to ephrinBs/EphBs.

Methods
Thermal hyperalgesia and mechanical allodynia were measured using radiant heat and von Frey filaments test. Immunofluorescence staining was used to detect the expression of p-MAPKs and of p-MAPKs/neuronal nuclei, or p-MAPKs/glial fibrillary acidic protein double label. C-Fos expression was determined by immunohistochemistry. The expression of p-MAPKs was also determined by Western blot assay.

Results
Intrathecal injection of ephrinB1-Fc produced a dose- and time-dependent thermal and mechanical hyperalgesia, accompanied by the increase of spinal p-MAPKs and c-Fos expression. Immunofluorescence staining revealed that p-MAPKs colocalized with the neuronal marker (neuronal nuclei) and the astrocyte marker (glial fibrillary acidic protein). Inhibition of MAPKs prevented and reversed pain behaviors and the increase of spinal c-Fos expression induced by intrathecal injection of ephrinB1-Fc. Inhibition of EphBs receptors by intrathecal injection of EphB1-Fc reduced formalin-induced inflammation and chronic constrictive injury-induced neuropathic pain behaviors accompanied by decreased expression of spinal p-MAPKs and c-Fos protein. Furthermore, pretreatment with MK-801, an N-methyl-d-aspartate receptor antagonist, prevented behavioral hyperalgesia and activation of spinal MAPKs induced by intrathecal injection of ephrinB1-Fc.

Conclusions
These results demonstrated that activation of MAPKs contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs.
Hydrocortisone Supplementation Enhances Hemodynamic Stability in Brain-dead Patients
Authors: Nicolas-Robin Armelle , Barouk Jérome D. , Amour Julien , Coriat Pierre , Riou Bruno , Langeron Olivier 
Published: April 2010

Background
Hemodynamic instability is frequent in brain-dead patients and may result, in part, from absolute or relative adrenal insufficiency. Corticosteroid supplementation is widely used to restore hemodynamic stability in septic shock and to reduce the time of shock resolution. The authors verified that supplementation with hydrocortisone may enhance hemodynamic stability in brain-dead patients.

Methods
All consecutive brain-dead patients with hypotension requiring vasopressor agents were included in this single-center noninterventional clinical observation study. Assessment of baseline and adrenocorticotropic hormone (ACTH)-stimulated plasma cortisol concentrations was performed. Immediately after, patients were systematically treated with a single intravenous injection of hydrocortisone (50 mg), and norepinephrine administration was adjusted every 15 min to maintain mean arterial pressure between 65 and 90 mmHg. Adrenal insufficiency was defined as baseline plasma cortisol concentration less than 15 microg/dl and/or delta plasma cortisol concentration less than 9 microg/dl. Patients were considered as ACTH responders when delta cortisol concentration was more than 9 microg/dl 30 min after ACTH injection.

Results
Among the 31 patients included, the incidence of adrenal insufficiency was 87% [95% CI, 70-96%]. A significant (> or =30%) decrease in norepinephrine dose was obtained 180 min after hydrocortisone injection in 18 (59%) patients, from 0.31 [0.16-0.44] microg . kg(-1) . min(-1) to 0.18 [0.10-0.24] microg . kg(-1) . min(-1) (P < 0.01). The incidence of hemodynamic response was greater in ACTH nonresponders than in ACTH responders: 86% versus 50%, respectively, P < 0.05.

Conclusions
Adrenal insufficiency with hemodynamic instability is frequent in brain-dead patients. After ACTH stimulation testing and hydrocortisone infusion, hemodynamic stability is enhanced especially in patients with true adrenal nonfunction.
Face Mask Ventilation in Edentulous Patients
Authors: Racine Stéphane X. , Solis Audrey , Hamou Nora Ait , Letoumelin Philippe , Hepner David L. , Beloucif Sadek , Baillard Christophe 
Published: April 2010

Background
In edentulous patients, it may be difficult to perform face mask ventilation because of inadequate seal with air leaks. Our aim was to ascertain whether the "lower lip" face mask placement, as a new face mask ventilation method, is more effective at reducing air leaks than the standard face mask placement.

Methods
Forty-nine edentulous patients with inadequate seal and air leak during two-hand positive-pressure ventilation using the ventilator circle system were prospectively evaluated. In the presence of air leaks, defined as a difference of at least 33% between inspired and expired tidal volumes, the mask was placed in a lower lip position by repositioning the caudal end of the mask above the lower lip while maintaining the head in extension. The results are expressed as mean +/- SD or median (25th-75th percentiles).

Results
Patient characteristics included age (71 +/- 11 yr) and body mass index (24 +/- 4 kg/m2). By using the standard method, the median inspired and expired tidal volumes were 450 ml (400-500 ml) and 0 ml (0-50 ml), respectively, and the median air leak was 400 ml (365-485 ml). After placing the mask in the lower lip position, the median expired tidal volume increased to 400 ml (380-490), and the median air leak decreased to 10 ml (0-20 ml) (P < 0.001 vs. standard method). The lower lip face mask placement with two hands reduced the air leak by 95% (80-100%).

Conclusions
In edentulous patients with inadequate face mask ventilation, the lower lip face mask placement with two hands markedly reduced the air leak and improved ventilation.
Effects on Brain Edema of Crystalloid and Albumin Fluid Resuscitation after Brain Trauma and Hemorrhage in the Rat
Authors: Jungner Mårten , Grände Per-Olof , Mattiasson Gustav , Bentzer Peter 
Published: April 2010

Background
It has been hypothesized that resuscitation with crystalloids after brain trauma increases brain edema compared with colloids, but previous studies on the subject have been inconclusive. To test this hypothesis, the authors compared groups resuscitated with either colloid or crystalloid.

Methods
After fluid percussion injury, rats were subjected to a controlled hemorrhage of 20 ml/kg and were randomized to 5% albumin at 20 ml/kg (A20), isotonic Ringer's acetate at 50 ml/kg (C50), or 90 ml/kg (C90). After 3 or 24 h, water content in the injured cortex was determined using a wet/dry weight method. Blood volume was calculated from plasma volume, measured by 125I-albumin dilution, and hematocrit. Oncotic pressure and osmolality were measured with osmometers.

Results
At 3 h, blood volume was equal in the A20 and C90 groups and lower in the C50 group. Oncotic pressure was reduced by 35-40% in the crystalloid groups and unchanged in the albumin group. Cortical water content in the A20 group was lower than in the C90 group (81.3 +/- 0.5% vs. 82.1 +/- 1.1%, P < 0.05), but it was not different from the C50 group (81.8 +/- 1.1%). At 24 h, oncotic pressure and blood volume were normalized in all groups, and cortical water content was significantly lower in the albumin group than in the crystalloid groups. Osmolality and arterial pressure were equal in all groups throughout the experiment.

Conclusions
When given to the same intravascular volume expansion, isotonic crystalloids caused greater posttraumatic brain edema than 5% albumin at 3 and 24 h after trauma.
Effects of Intrathecal Ketorolac on Human Experimental Pain
Authors: Eisenach James C. , Curry Regina , Tong Chuanyao , Houle Timothy T. , Yaksh Tony L. 
Published: April 2010

Background
Nonsteroidal antiinflammatory drugs, the most commonly used analgesics, reduce pain not only by inhibiting cyclooxygenase at peripheral sites of inflammation but also by potentially inhibiting cyclooxygenase in the central nervous system, especially the spinal cord. Animal studies suggest that products of cyclooxygenase in the spinal cord do not alter pain responses to acute noxious stimuli but reduce pain and sensitization after peripheral inflammation. We used a spinal injection of small doses of the cyclooxygenase inhibitor ketorolac to survey the role of spinal cyclooxygenase in human experimental pain and hypersensitivity states.

Methods
After regulatory agency approval and informed consent, we examined the effect of 2.0 mg intrathecal ketorolac in 41 healthy volunteers to acute noxious thermal stimuli in normal skin and to mechanical stimuli in skin sensitized by topical capsaicin or ultraviolet burn. We also examined the effect of intravenous ketorolac.

Results
Intrathecal ketorolac reduced hypersensitivity when it was induced by a combination of ultraviolet burn plus intermittent heat and, according to one of the two analytical strategies, when it was induced by ultraviolet burn alone.

Conclusions
These data suggest a more limited role for spinal cord cyclooxygenase in human pain states than predicted by studies in animals.
Role of Spinal Cyclooxygenase in Human Postoperative and Chronic Pain
Authors: Eisenach James C. , Curry Regina , Rauck Richard , Pan Peter , Yaksh Tony L. 
Published: April 2010

Background
Nonsteroidal antiinflammatory drugs are commonly used to treat postoperative and chronic pain. Animal studies suggest that these drugs act, in part, by blocking prostaglandin production in the spinal cord. The authors tested intrathecal ketorolac in patients with chronic or postoperative pain.

Methods
After approval of the institutional review board and the Food and Drug Administration, three clinical studies were performed. First, 15 patients receiving chronic intrathecal morphine received 0.5-2.0 mg of intrathecal ketorolac. Second, 12 patients receiving chronic intrathecal morphine received, in a double-blinded, randomized, cross-over design, intrathecal saline or 2.0 mg of ketorolac, with pain intensity as the primary outcome measure. Third, 30 patients undergoing total vaginal hysterectomy received, in a double-blinded, randomized, controlled design, intrathecal saline or 2.0 mg of ketorolac, with bupivacaine with time to first morphine dose after surgery as the primary outcome measure.

Results
Patients with chronic pain had many symptoms before intrathecal injection, without worsening of these symptoms from ketorolac. Pain intensity was reduced by intrathecal ketorolac, but this did not differ from placebo. In the first study, pain was reduced by intrathecal ketorolac in patients with high cerebrospinal fluid prostaglandin E2 concentrations but not in those with normal concentrations. Intrathecal ketorolac did not alter time to first morphine after surgery.

Conclusions
Intrathecal ketorolac did not relieve chronic pain or extend anesthesia or analgesia from intrathecal bupivacaine administered at the beginning of surgery. Under the conditions of these studies, it seems that spinal cylcooxygenase activity does not contribute to chronic or postoperative pain.
The Changing Fate of a Secretory Glycoprotein in Developing Maize Endosperm
Authors: Arcalis Elsa , Stadlmann Johannes , Marcel Sylvain , Drakakaki Georgia , Winter Verena , Rodriguez Julian , Fischer Rainer , Altmann Friedrich , Stoger Eva 
Published: April 2010

Abstract
Zeins are the major storage proteins in maize (Zea mays) endosperm, and their accumulation in zein bodies derived from the endoplasmic reticulum is well characterized. In contrast, relatively little is known about post-Golgi compartments or the trafficking of vacuolar proteins in maize endosperm, specifically the presence of globulins in structures resembling protein storage vacuoles that appear in early to mid-stage seed development. We investigated this pathway by expressing and analyzing a recombinant reporter glycoprotein during endosperm maturation, using a combination of microscopy and sensitive glycopeptide analysis. Specific N-glycan acceptor sites on the protein were followed through the stages of grain development, revealing a shift from predominantly paucimannosidic vacuolar glycoforms to predominantly trimmed glycan structures lacking fucose. This was accompanied by a change in the main subcellular localization of the protein from large protein storage vacuole-like post-Golgi organelles to the endoplasmic reticulum and zein bodies. The endogenous storage proteins corn α-globulin and corn legumin-1 showed a similar spatiotemporal profile both in transgenic plants expressing the reporter glycoprotein and in wild-type plants. This indicates that the shift of the intracellular trafficking route, as observed with our reporter glycoprotein, may be a common strategy in maize seed development.
Robin: An Intuitive Wizard Application for R-Based Expression Microarray Quality Assessment and Analysis
Authors: Lohse Marc , Nunes-Nesi Adriano , Krüger Peter , Nagel Axel , Hannemann Jan , Giorgi Federico M. , Childs Liam , Osorio Sonia , Walther Dirk , Selbig Joachim , Sreenivasulu Nese , Stitt Mark , Fernie Alisdair R. , Usadel Björn 
Published: April 2010

AbstractThe wide application of high-throughput transcriptomics using microarrays has generated a plethora of technical platforms, data repositories, and sophisticated statistical analysis methods, leaving the individual scientist with the problem of choosing the appropriate approach to address a biological question. Several software applications that provide a rich environment for microarray analysis and data storage are available (e.g. GeneSpring, EMMA2), but these are mostly commercial or require an advanced informatics infrastructure. There is a need for a noncommercial, easy-to-use graphical application that aids the lab researcher to find the proper method to analyze microarray data, without this requiring expert understanding of the complex underlying statistics, or programming skills. We have developed Robin, a Java-based graphical wizard application that harnesses the advanced statistical analysis functions of the R/BioConductor project. Robin implements streamlined workflows that guide the user through all steps of two-color, single-color, or Affymetrix microarray analysis. It provides functions for thorough quality assessment of the data and automatically generates warnings to notify the user of potential outliers, low-quality chips, or low statistical power. The results are generated in a standard format that allows ready use with both specialized analysis tools like MapMan and PageMan and generic spreadsheet applications. To further improve user friendliness, Robin includes both integrated help and comprehensive external documentation. To demonstrate the statistical power and ease of use of the workflows in Robin, we present a case study in which we apply Robin to analyze a two-color microarray experiment comparing gene expression in tomato (Solanum lycopersicum) leaves, flowers, and roots.
DNA Is Taken Up by Root Hairs and Pollen, and Stimulates Root and Pollen Tube Growth
Authors: Paungfoo-Lonhienne Chanyarat , Lonhienne Thierry G.A. , Mudge Stephen R. , Schenk Peer M. , Christie Michael , Carroll Bernard J. , Schmidt Susanne 
Published: April 2010

Abstract
Phosphorus (P) enters roots as inorganic phosphate (Pi) derived from organic and inorganic P compounds in the soil. Nucleic acids can support plant growth as the sole source of P in axenic culture but are thought to be converted into Pi by plant-derived nucleases and phosphatases prior to uptake. Here, we show that a nuclease-resistant analog of DNA is taken up by plant cells. Fluorescently labeled S-DNA of 25 bp, which is protected against enzymatic breakdown by its phosphorothioate backbone, was taken up and detected in root cells including root hairs and pollen tubes. These results indicate that current views of plant P acquisition may have to be revised to include uptake of DNA into cells. We further show that addition of DNA to Pi-containing growth medium enhanced the growth of lateral roots and root hairs even though plants were P replete and had similar biomass as plants supplied with Pi only. Exogenously supplied DNA increased length growth of pollen tubes, which were studied because they have similar elongated and polarized growth as root hairs. Our results indicate that DNA is not only taken up and used as a P source by plants, but ironically and independent of Pi supply, DNA also induces morphological changes in roots similar to those observed with P limitation. This study provides, to our knowledge, first evidence that exogenous DNA could act nonspecifically as signaling molecules for root development.
Inhibition of Auxin Transport from the Ovary or from the Apical Shoot Induces Parthenocarpic Fruit-Set in Tomato Mediated by Gibberellins
Authors: Serrani Juan Carlos , Carrera Esther , Ruiz-Rivero Omar , Gallego-Giraldo Lina , Peres LÁzaro EustÁquio Pereira , García-Martínez José Luis 
Published: April 2010

AbstractFruit-set in tomato (Solanum lycopersicum) depends on gibberellins and auxins (GAs). Here, we show, using the cv MicroTom, that application of N-1-naphthylphthalamic acid (NPA; an inhibitor of auxin transport) to unpollinated ovaries induced parthenocarpic fruit-set, associated with an increase of indole-3-acetic acid (IAA) content, and that this effect was negated by paclobutrazol (an inhibitor of GA biosynthesis). NPA-induced ovaries contained higher content of GA1 (an active GA) and transcripts of GA biosynthetic genes (SlCPS, SlGA20ox1, and -2). Interestingly, application of NPA to pollinated ovaries prevented their growth, potentially due to supraoptimal IAA accumulation. Plant decapitation and inhibition of auxin transport by NPA from the apical shoot also induced parthenocarpic fruit growth of unpollinated ovaries. Application of IAA to the severed stump negated the plant decapitation effect, indicating that the apical shoot prevents unpollinated ovary growth through IAA transport. Parthenocarpic fruit growth induced by plant decapitation was associated with high levels of GA1 and was counteracted by paclobutrazol treatment. Plant decapitation also produced changes in transcript levels of genes encoding enzymes of GA biosynthesis (SlCPS and SlGA20ox1) in the ovary, quite similar to those found in NPA-induced fruits. All these results suggest that auxin can have opposing effects on fruit-set, either inducing (when accumulated in the ovary) or repressing (when transported from the apical shoot) that process, and that GAs act as mediators in both cases. The effect of NPA application and decapitation on fruit-set induction was also observed in MicroTom lines bearing introgressed DWARF and SELF-PRUNING wild-type alleles.
Identification of QTL for dorso‐caudal chronic pleuritis in 12 crossbred porcine families
Authors: Gregersen V. R. , Sørensen K. K. , Christensen O. F. , Busch M. E. , Vingborg R. K. K. , Velander I. H. , Lund M. S. , Bendixen C. 
Published: April 2010

SummaryPleuropneumonia is a major problem in pig production. At the time of slaughter, chronic pleuritis (CP) developed from pleuropneumonia is a common finding, and breeding for a reduced incidence of CP using marker‐assisted selection (MAS) would be advantageous. Before applying MAS, quantitative trait loci (QTL) or markers associated with the prevalence of CP should be identified. In this study, 7470 pigs from crosses between 12 Danish Duroc boars and 604 sows (Danish Landrace × Danish Large White) were evaluated for CP located on the dorso‐caudal part of the lungs. Quantitative trait loci were identified within boar families using both a Binomial logistic regression method and a chi‐square test of association. Significant QTL for CP were detected onSus scrofachromosomes (SSC) 2, 8, 12, 13, 14 and 18 using both methods. One QTL on SSC 8 was also detected across families. For the QTL identified within families, the odds‐ratio of having CP was approximately twice as high for the unfavourable allele compared to the favourable one. These QTL and closely linked markers show promise for the development of gene‐specific markers associated with a reduced incidence of CP located on the dorso‐caudal part of the lungs.