The polytopic membrane protein Rhomboid-1 promotes the cleavage of the membrane-anchored TGFα-like growth factor Spitz, allowing it to activate the
Drosophila EGF receptor. Until now, the mechanism ...of this key signaling regulator has been obscure, but our analysis suggests that Rhomboid-1 is a novel intramembrane serine protease that directly cleaves Spitz. In accordance with the putative Rhomboid active site being in the membrane bilayer, Spitz is cleaved within its transmembrane domain, and thus is, to our knowledge, the first example of a growth factor activated by regulated intramembrane proteolysis. Rhomboid-1 is conserved throughout evolution from archaea to humans, and our results show that a human Rhomboid promotes Spitz cleavage by a similar mechanism. This growth factor activation mechanism may therefore be widespread.
Diacylglycerol-lactone (DAG-lactone) libraries generated by a solid-phase approach using IRORI technology produced a variety of unique biological activities. Subtle differences in chemical diversity ...in two areas of the molecule, the combination of which generates what we have termed “chemical zip codes”, are able to transform a relatively small chemical space into a larger universe of biological activities, as membrane-containing organelles within the cell appear to be able to decode these “chemical zip codes”. It is postulated that after binding to protein kinase C (PKC) isozymes or other nonkinase target proteins that contain diacylglycerol responsive, membrane interacting domains (C1 domains), the resulting complexes are directed to diverse intracellular sites where different sets of substrates are accessed. Multiple cellular bioassays show that DAG-lactones, which bind in vitro to PKCα to varying degrees, expand their biological repertoire into a larger domain, eliciting distinct cellular responses.
Two new metal–organic frameworks, M2(dobpdc) (M = Zn (1), Mg (2); dobpdc4– = 4,4′-dioxido-3,3′-biphenyldicarboxylate), adopting an expanded MOF-74 structure type, were synthesized via solvothermal ...and microwave methods. Coordinatively unsaturated Mg2+ cations lining the 18.4-Å-diameter channels of 2 were functionalized with N,N′-dimethylethylenediamine (mmen) to afford Mg2(dobpdc)(mmen)1.6(H2O)0.4 (mmen-Mg2(dobpdc)). This compound displays an exceptional capacity for CO2 adsorption at low pressures, taking up 2.0 mmol/g (8.1 wt %) at 0.39 mbar and 25 °C, conditions relevant to removal of CO2 from air, and 3.14 mmol/g (12.1 wt %) at 0.15 bar and 40 °C, conditions relevant to CO2 capture from flue gas. Dynamic gas adsorption/desorption cycling experiments demonstrate that mmen-Mg2(dobpdc) can be regenerated upon repeated exposures to simulated air and flue gas mixtures, with cycling capacities of 1.05 mmol/g (4.4 wt %) after 1 h of exposure to flowing 390 ppm CO2 in simulated air at 25 °C and 2.52 mmol/g (9.9 wt %) after 15 min of exposure to flowing 15% CO2 in N2 at 40 °C. The purity of the CO2 removed from dry air and flue gas in these processes was estimated to be 96% and 98%, respectively. As a flue gas adsorbent, the regeneration energy was estimated through differential scanning calorimetry experiments to be 2.34 MJ/kg CO2 adsorbed. Overall, the performance characteristics of mmen-Mg2(dobpdc) indicate it to be an exceptional new adsorbent for CO2 capture, comparing favorably with both amine-grafted silicas and aqueous amine solutions.
Clinical and Imaging Features of Fludarabine Neurotoxicity Lee, Michael S; McKinney, Alexander M; Brace, Jeffrey R ...
Journal of neuro-ophthalmology,
2010-March, 2010-Mar, 2010-03-00, 20100301, Letnik:
30, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Neurotoxicity from intravenous fludarabine is a rare but recognized clinical entity. Its brain imaging features have not been extensively described. Three patients received 38.5 mg or 40 mg/m per day ...fludarabine in a 5-day intravenous infusion before bone marrow transplantation in treatment of hematopoietic malignancies. Several weeks later, each patient developed progressive neurologic decline, including retrogeniculate blindness, leading to coma and death. Brain MRI showed progressively enlarging but mild T2/FLAIR hyperintensities in the periventricular white matter. The lesions demonstrated restricted diffusion but did not enhance. Because the neurotoxicity of fludarabine appears long after exposure, neurologic decline in this setting is likely to be attributed to opportunistic disease. However, the imaging features are distinctive in their latency and in being mild relative to the profound clinical features. The safe dose of fludarabine in this context remains controversial.
Eccrine hidrocystomas are benign, small, cystic growths that characteristically occur on the eyelids, but away from the lid margin. The size of these growths are generally reported as being between 1 ...and 5 mm. The case of a patient with a very large hidrocystoma of the eyelid with a previously undescribed pedunculated morphology is presented. The pathologic features of this entity and the different diagnosis of cystic lesions are also discussed.
We present the fifth edition of the Sloan Digital Sky Survey (SDSS) Quasar Catalog, which is based upon the SDSS Seventh Data Release. The catalog, which contains 105,783 spectroscopically confirmed ...quasars, represents the conclusion of the SDSS-I and SDSS-II quasar survey. The catalog consists of the SDSS objects that have luminosities larger than Mi = --22.0 (in a cosmology with H 0 = 70 km s--1 Mpc--1, Delta *W M = 0.3, and Delta *W Delta *L = 0.7), have at least one emission line with FWHM larger than 1000 km s--1 or have interesting/complex absorption features, are fainter than i 15.0, and have highly reliable redshifts. The catalog covers an area of 9380 deg2. The quasar redshifts range from 0.065 to 5.46, with a median value of 1.49; the catalog includes 1248 quasars at redshifts greater than 4, of which 56 are at redshifts greater than 5. The catalog contains 9210 quasars with i < 18; slightly over half of the entries have i < 19. For each object the catalog presents positions accurate to better than 01 rms per coordinate, five-band (ugriz) CCD-based photometry with typical accuracy of 0.03 mag, and information on the morphology and selection method. The catalog also contains radio, near-infrared, and X-ray emission properties of the quasars, when available, from other large-area surveys. The calibrated digital spectra cover the wavelength region 3800-9200 A at a spectral resolution of 2000; the spectra can be retrieved from the SDSS public database using the information provided in the catalog. Over 96% of the objects in the catalog were discovered by the SDSS. We also include a supplemental list of an additional 207 quasars with SDSS spectra whose archive photometric information is incomplete.
Simultaneous 10 kHz repetition-rate tomographic particle image velocimetry, hydroxyl planar laser-induced fluorescence (OH PLIF), and formaldehyde (CH
2
O) PLIF were used to study the structure and ...dynamics of turbulent premixed flames. The flames investigated span from the classically defined corrugated flamelet regime to conditions at which broadened and/or broken flamelets are expected. Methods are presented for determining 3D flame topologies from the Mie scattering tomography and for tracking features through space and time using theoretical Lagrangian particles. Substantial broadening of the CH
2
O region is observed with increasing turbulence intensity. However, OH production remains rapid, and the region of OH and CH
2
O overlap remains thin. Local flame speeds exceeding three times the laminar flame speed are observed in regions of flame–flame interaction. Furthermore, a method of tracking fluid residence time within the CH
2
O layer is presented and shows that residence time decreases at higher turbulence intensity despite the broader distribution of the CH
2
O, indicating an increase in local reaction rate.
Following gastrectomy, the remnant oxyntic mucosa is at increased risk of developing adenocarcinoma. Alkaline pancreaticoduodenal reflux, carcinogen production from intragastric bacterial overgrowth, ...denervation, and devascularization have been implicated in this malignant transformation. Recent reports have described a novel spasmolytic polypeptide (SP) expressing metaplastic lineage designated as SPEM. This lineage has been identified in the mucosa surrounding gastric adenocarcinomas, and SP staining has been observed in the cells of surface dysplasia and invasive malignancy. In this study we describe 19 cases of remnant gastric adenocarcinoma from Japan. In addition, we studied surveillance biopsies in 90 patients who underwent antrectomy for carcinoma. SPEM was identified in the mucosa surrounding 88% of the remnant cancers, as well as in 61% of the surveillance biopsies. In the malignant resections, 67% of the surface dysplasia displayed SP positive cells, and 25% revealed SP immunostaining within invasive malignant cells. These findings implicate SPEM as a potential precursor lesion of gastric adenocarcinoma.
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