Fore-knowledge of the secondary metabolic potential of cultivated and previously uncultivated microorganisms can potentially facilitate the process of natural product discovery. By combining ...sequence-based knowledge with biochemical precedent, translated gene sequence data can be used to rapidly derive structural elements encoded by secondary metabolic gene clusters from microorganisms. These structural elements provide an estimate of the secondary metabolic potential of a given organism and a starting point for identification of potential lead compounds in isolation/structure elucidation campaigns. The accuracy of these predictions for a given translated gene sequence depends on the biochemistry of the metabolite class, similarity to known metabolite gene clusters, and depth of knowledge concerning its biosynthetic machinery. This chapter introduces methods for prediction of structural elements for two well-studied classes: modular polyketides and nonribosomally encoded peptides. A bioinformatics tool is presented for rapid preliminary analysis of these modular systems, and prototypical methods for converting these analyses into substructural elements are described.
The purpose of this study was to determine the relative importance of blood vessels (hemangiogenesis) versus lymphatic vessels (lymphangiogenesis) in mediating immunological responses after ...transplantation. Using the murine model of corneal transplantation, graft survival was compared in differentially prevascularized and avascular recipient beds. Donor corneas (C57BL/6) were transplanted into uninflamed or inflamed avascular, prehemvascularized only or prehemvascularized and prelymphvascularized recipient murine eyes (BALB/C). Selective inhibition of lymphangiogenesis was achieved using antivascular endothelial growth factor receptor 3 Abs and anti-integrin alpha5 small molecules. Grafts placed into only prehemvascularized recipient beds had a similarly good graft survival compared with grafts placed into completely avascular, normal recipients, whereas the pre-existence of lymphatic vessels significantly deteriorated corneal graft survival (p < 0.05). Lymphatic vessels seem to contribute significantly to graft rejection after (corneal) transplantation. That may allow for selective, temporary, perioperative antilymphangiogenic treatment to promote graft survival without affecting blood vessels, even after solid organ transplantation.
The largest accumulations of rhyolitic melt in the upper crust occur in voluminous silicic crystal mushes, which sometimes erupt as unzoned, crystal-rich ignimbrites, but are most frequently ...preserved as granodioritic batholiths. After approximately 40–50% crystallization, magmas of intermediate composition (andesite–dacite) typically contain high-SiO2 interstitial melt, similar to crystal-poor rhyolites commonly erupted in mature arc and continental settings. This paper analyzes the feasibility of system-wide extraction of this melt from the mush, a mechanism that can rationalize a number of observations in both the plutonic and volcanic record, such as: (1) abrupt compositional gaps in ignimbrites; (2) the presence of chemically highly evolved bodies at the roof of subvolcanic batholiths; (3) the observed range of ages (up to 200–300 ka) recorded by zircons in silicic magmas; (4) extensive zones of low P-wave velocity in the shallow crust under active silicic calderas. We argue that crystal–melt segregation occurs by a combination of several processes (hindered settling, micro-settling, compaction) once convection is hampered as the rheological locking point of the crystal–melt mixture (≥50 vol. % crystals) is attained. We constrain segregation rates by using hindered settling velocities and compaction rates as end-members. Time scales estimated for the formation of >500 km3 of crystal-poor rhyolite range from 104 to 105 years, within the estimated residence times of mushes in the upper crust (>105 years, largely based on U/Th and U/Pb dating). This model provides an integrated picture of silicic magmatism, linking the evolution of plutonic and volcanic systems until storage in the upper crust, where granitoids become the leftovers from rhyolitic eruptions.
To analyze the incidence and clinical course of graft rejection episodes after Descemet membrane endothelial keratoplasty (DMEK).
Retrospective analysis of a consecutive, interventional case series.
...One thousand eyes that underwent DMEK from July 2011 through August 2015 at the Department of Ophthalmology, University of Cologne.
All cases with follow-up of at least 1 month were included (mean follow-up, 18.5 months). Patients with a graft rejection episode were followed up for 1 additional year.
Incidence of graft rejection, best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), endothelial cell density (ECD), and need for regraft.
Nine hundred five cases met the inclusion criteria. A graft rejection episode developed in 12 patients (estimated probability of rejection at 1 year, 0.9%; at 2 years, 2.3%; at 4 years, 2.3%). At time of rejection, 9 of 12 patients had stopped corticosteroids. Five patients were symptomatic and 7 did not note the rejection episode. Intensified topical corticosteroid therapy was started immediately after diagnosis of rejection. Two eyes decompensated and required a regraft, whereas the remaining 10 eyes required no regraft (BSCVA, 0.27±0.28 logarithm of the minimum angle of resolution logMAR; CCT, 554.1±39.1 μm at last visit before rejection vs. BSCVA, 0.21±0.15 logMAR; CCT, 540.0±15.0 μm 3 months after rejection). One year after the rejection episodes, BSCVA and CCT in these eyes remained unchanged when compared with the last visit before rejection (BSCVA, 0.15±0.11 logMAR; CCT, 533.8±26.0 μm). Significant changes were observed for ECD values (1741±274.5 cells/mm
at last visit before rejection vs. 1356±380.3 cells/mm
after 3 months P = 0.04 and 1290±359.0 cells/mm
after 1 year P = 0.01).
The risk for graft rejection after DMEK is low, and an even smaller minority requires a regraft. After intensified local corticosteroid therapy, most patients show stable visual acuity and CCT, although ECD decreases. The occurrence of immune reactions up to 2 years after surgery predominantly in patients not receiving corticosteroids supports the prolonged use of corticosteroids after DMEK.
The mechanics of shallow magma reservoir outgassing Parmigiani, A.; Degruyter, W.; Leclaire, S. ...
Geochemistry, geophysics, geosystems : G3,
August 2017, 2017-08-00, 20170801, Letnik:
18, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Magma degassing fundamentally controls the Earth's volatile cycles. The large amount of gas expelled into the atmosphere during volcanic eruptions (i.e., volcanic outgassing) is the most obvious ...display of magmatic volatile release. However, owing to the large intrusive:extrusive ratio, and considering the paucity of volatiles left in intrusive rocks after final solidification, volcanic outgassing likely constitutes only a small fraction of the overall mass of magmatic volatiles released to the Earth's surface. Therefore, as most magmas stall on their way to the surface, outgassing of uneruptible, crystal‐rich magma storage regions will play a dominant role in closing the balance of volatile element cycling between the mantle and the surface. We use a numerical approach to study the migration of a magmatic volatile phase (MVP) in crystal‐rich magma bodies (“mush zones”) at the pore scale. Our results suggest that buoyancy‐driven outgassing is efficient over crystal volume fractions between 0.4 and 0.7 (for mm‐sized crystals). We parameterize our pore‐scale results for MVP migration in a thermomechanical magma reservoir model to study outgassing under dynamical conditions where cooling controls the evolution of the proportion of crystal, gas, and melt phases and to investigate the role of the reservoir size and the temperature‐dependent viscoelastic response of the crust on outgassing efficiency. We find that buoyancy‐driven outgassing allows for a maximum of 40–50% volatiles to leave the reservoir over the 0.4–0.7 crystal volume fractions, implying that a significant amount of outgassing must occur at high crystal content (>0.7) through veining and/or capillary fracturing.
Key Points
Outgassing potential of a magma reservoir is a strong function of its crystal content
Outgassing efficiency is also modulated by mechanical coupling between reservoir and crust
Simulations that consider both aspects reveal that the majority of exsolved volatiles is released at intermediate to high crystallinity
Purpose To evaluate visual outcome and endothelial cell survival after Descemet membrane endothelial keratoplasty (DMEK) in comparison with Descemet stripping automated endothelial keratoplasty ...(DSAEK). Design Single-center, retrospective, consecutive case series. Methods Thirty-eight eyes of 38 consecutive patients undergoing DMEK, who completed a 6-month follow-up, were compared with 35 eyes of 35 consecutive patients undergoing DSAEK for Fuchs endothelial dystrophy or pseudophakic bullous keratopathy. Main outcome measures included best-corrected visual acuity (in logarithm of the minimal angle of resolution logMAR units) and endothelial cell density within a 6-month follow-up. Results Best-corrected visual acuity increased from 0.70 ± 0.48 logMAR and 0.75 ± 0.32 logMAR before surgery to 0.21 ± 0.14 logMAR and 0.48 ± 0.19 logMAR 3 months after DMEK and DSAEK ( P < .001), respectively, and to 0.17 ± 0.12 logMAR and 0.36 ± 0.15 logMAR 6 months after DMEK and DSAEK ( P < .001), respectively. Endothelial cell density decreased from 2575 ± 260 cells/mm2 and 2502 ± 220 cells/mm2 before surgery to 1498 ± 244 cells/mm2 and 1778 ± 420 cells/mm2 3 months after DMEK and DSAEK ( P < .001), respectively, and to 1520 ± 299 cells/mm2 and 1532 ± 495 cells/mm2 6 months after DMEK and DSAEK ( P = .483), respectively. Central corneal thickness decreased from 652 ± 92 μm before surgery to 517 ± 45 μm 6 months after DMEK, and from 698 ± 137 μm before surgery to 618 ± 66 μm 6 months after DSAEK. Conclusions DMEK provided faster and more complete visual rehabilitation when compared with DSAEK. However, there were no significant differences concerning endothelial cell survival within a 6-month follow-up.
Microbial genome mining is a rapidly developing approach to discover new and novel secondary metabolites for drug discovery. Many advances have been made in the past decade to facilitate genome ...mining, and these are reviewed in this Special Issue of the Journal of Industrial Microbiology and Biotechnology. In this Introductory Review, we discuss the concept of genome mining and why it is important for the revitalization of natural product discovery; what microbes show the most promise for focused genome mining; how microbial genomes can be mined; how genome mining can be leveraged with other technologies; how progress on genome mining can be accelerated; and who should fund future progress in this promising field. We direct interested readers to more focused reviews on the individual topics in this Special Issue for more detailed summaries on the current state-of-the-art.
Lamellar techniques for selective replacement of diseased corneal structures have recently been improved. Descemet membrane endothelial keratoplasty (DMEK) allows the sole replacement of the ...endothelium--Descemet membrane layer (EDM). However, wide-spread use of DMEK is currently limited because of problems with donor preparation namely the tearing of the Descemet membrane and the difficulty to unfold the EDM graft in the anterior chamber (AC).
A standardized DMEK procedure that allows safe preparation of EDM, atraumatic introduction of EDM into the AC, reliable orientation of EDM during surgery, and stepwise unfolding within the AC is described in 80 patients. Visual acuity and corneal endothelial cell density were assessed.
A stepwise approach using a novel bimanual underwater technique to harvest EDM from donor corneal buttons allows reproducible generation of grafts without tearing the Descemet membrane. Injection of the EDM roll into the AC is achieved by use of a standard injector cartridge, whereas the depth of AC is maintained by an irrigation handpiece. Marks at the margin of EDM allow orientation. Finally, unfolding EDM in the AC is achieved by sequential use of water jets and air bubbles. In the early phase of the learning curve, 4 patients were regrafted because of graft failure. Endothelial cell density decreased from 2600 6 252 to 1526 6 341 cells per square millimeter 1 month after DMEK.
A novel technique for graft preparation and EDM injection results in improved safety with a high rate of successful DMEKs.
Silicic calderas globally tend to record a cyclic magmatic, structural, and eruptive evolutionary progression. Some calderas are polycyclic, involving multiple catastrophic collapses in the same ...approximate location. Here we discuss five examples from well-studied, geologically-young and active magmatic systems: The Kos-Nisyros Volcanic Complex (Greece), Long Valley (USA), Campi Flegrei (Southern Italy), Rabaul (Papua New Guinea), and Okataina (New Zealand) in order to gain insights on the inner workings of caldera systems during the build up to and recovery from large explosive eruptions. We show that the sub-caldera magmatic system evolves through a series of processes, here collectively termed “caldera cycle”, that are common to monocyclic and polycyclic calderas. In the case of polycyclic calderas, they accompany the transition from one caldera-forming eruption to the next. The caldera cycle comprises (1) the period of pre-collapse activity (incubation, maturation, widespread presence of a magmatic volatile phase), (2) the catastrophic caldera-forming (CCF) eruption, and (3) post-collapse recovery (resurgence, renewed eruptions, subsequent maturation) or the possible cessation of the cycle. The incubation phase corresponds to a period of thermal maturation of the crust, during which eruptions are frequent and of small volume due to the limited capability of reservoirs to grow. During the maturation phase, magma reservoirs gradually grow, coalesce, homogenize, magmas differentiate, and eruption frequency decreases. The system transitions into the fermentation phase once an exsolved magmatic volatile phase is continuously present in the reservoir, thereby increasing the compressibility of the magma and instigating a period of runaway growth of the reservoir. A CCF eruption at the end of the fermentation phase could be the concatenated result of multiple magmatic processes (including magma recharge, volatile exsolution, and crystal mush remelting) pressurizing the reservoir, while external factors (e.g., tectonic processes) can also play a role. Postcaldera eruptions, subvolcanic intrusions, and hydrothermal activity typically continue, even if the magma supply wanes. If, however, magma supply at depth remains substantial, the system may recover, initially erupting the remobilized remains of the CCF reservoir and/or new recharging magmas until a shallow reservoir starts to grow and mature again. Placing other calderas worldwide within this framework would enable to test the robustness of the proposed framework, deepen the understanding of what controls the duration of a cycle and its individual phases, and refine the petrologic, geophysical, and unrest symptoms that are characteristic of the state of a system.
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