Tuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the
TSC1
or
TSC2
gene, two key regulators of the mechanistic target of the rapamycin complex pathway. ...Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC. Recently, gene expression studies provided evidence that the immune system, the MAPK pathway and extracellular matrix organization play an important role in SEGA development. However, the precise mechanisms behind the gene expression changes in SEGA are still largely unknown, providing a potential role for DNA methylation. We investigated the methylation profile of SEGAs using the Illumina Infinium HumanMethylation450 BeadChip (SEGAs
n
= 42, periventricular control
n
= 8). The SEGA methylation profile was enriched for the adaptive immune system, T cell activation, leukocyte mediated immunity, extracellular structure organization and the ERK1 & ERK2 cascade. More interestingly, we identified two subgroups in the SEGA methylation data and show that the differentially expressed genes between the two subgroups are related to the MAPK cascade and adaptive immune response. Overall, this study shows that the immune system, the MAPK pathway and extracellular matrix organization are also affected on DNA methylation level, suggesting that therapeutic intervention on DNA level could be useful for these specific pathways in SEGA. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway and could potentially hold predictive information on target treatment response.
Offshore observations at modern ocean-margin subduction zones (OMSZs) reveal that bodies of accreted material are commonly volumetrically small or missing, that crustal thinning and subsidence (3-5 ...km) has occurred, and that most trench axes lie close (5-30 km) to the seaward tapering edge of coastal basement rock. Onshore mapping commonly documents missing or only narrow terranes of former forearc rock and the inboard migration of the arc magmatic front. These observations are evidence that subduction is accompanied by the removal of sediment and crustal material from the submerged forearc by the kindred tectonic processes, respectively, of sediment subduction and subduction erosion. Subduction erosion truncates the margin (migrates the trench inboard) at ∼2.5 km/Ma. Onshore observations at ancient crust-suturing subduction zones (CSSZs) imply that collisional suturing is accompanied by sediment subduction and truncation of both upper and lower plates. During a protracted period of suturing (20-50 million years), a 100-200 km wide (or wider) band of the seaward edge of each plate can be removed subductively. Truncation of the upper plate is effected by subduction erosion, and that of the lower plate by the necking and break-off of its subducted edge. The average linear rate of crustal loss for each plate is estimated at ∼1.5 km/Ma, or ∼3 km/Ma combined. Because significant crustal loss occurs before and during tectonic fusing of colliding crustal blocks, structures and rock bodies that might be expected to record a former OMSZ and the formation of a CSSZ may be absent, unimpressively small, or preserved only as exhumed masses of once deeply subducted material.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The convergent margin off the Pacific coast of the Nicoya Peninsula of Costa Rica exhibits evidence for subduction erosion caused by the underthrusting Cocos plate. Critical evidence for efficacy of ...this process was recovered at the Ocean Drilling Program (ODP) drilling Site 1042 (Leg 170), positioned ∼7 km landward of the Middle America trench axis off the Nicoya Peninsula. The primary drilling objective at this site was to identify the age and origin of a regionally extensive and prominent seismic discontinuity, the so‐called base‐of‐slope sediment (BOSS) horizon or surface. The BOSS horizon, which can be traced landward from near the trench to the Nicoya coastal area and parallel to it for hundreds of kilometers, separates a low‐velocity (∼ 2.0–2.5 km s−1) sequence of slope sediment, from an underlying sequence of much higher‐velocity (>4–4.5 km s−1) rock. Site 1042 reached the acoustically defined BOSS horizon at a below sea level depth of ∼ 3900 m and yielded a carbonate‐cemented calcarenitic breccia of early‐middle Miocene age. Sedimentological, geochemical, paleontological, and cement paragenesis data document that the breccia accumulated in a shallow water depositional environment. On the basis of coastal exposures, the BOSS horizon, as a margin‐wide geologic interface, can be temporally and lithostratigraphically correlated to a regional angular unconformity. This unconformity, known as the Mal Pais unconformity, separates Neogene and younger shelf‐to‐littoral beds from the underlying mafic units of the Mesozoic Nicoya Complex and Cretaceous and early Tertiary sedimentary sequences. At Site 1042 it is inferred that tectonism caused the vertical subsidence of the early Neogene breccia from a shallow to a deep water setting. The Mal Pais unconformity of the BOSS horizon thus connects the rock fabric of the outermost part of margin to that of coastal Nicoya and implies that in the early Neogene the Nicoya shelf extended seaward to near the present trench axis. This circumstance requires that the early Neogene trench axis was at least 50 km seaward of where it is now located. The long‐term effects of subduction erosion, similar to those described for the scientifically drilled Japan, Tonga, and Peru margins, best account for offshore and onshore evidence for a post‐Paleogene history of crustal thinning and landward trench migration of Costa Rica's Pacific margin. During the past 16–17 Myr the calculated mass removal and landward migration rates are 34–36 km³ Myr−1 km−1 of margin, and 3 km Myr−1, respectively. These values are similar to those found for other Pacific margins dominated by nonaccretionary subduction zone processes.
The Defense Advanced Research Projects Agency's Revolutionizing Prosthetics program demonstrated the potential for neural interface technologies, enabling patients to control and feel a prosthetic ...arm and hand, and even pilot an aircraft in simulation. These landmark achievements required invasive, chronically implanted penetrating electrode arrays, which are fundamentally incompatible with applications for the able-bodied warfighter or for long-term clinical applications. Noninvasive neural recording approaches have not been as effective, suffering from severe limitations in temporal and spatial resolution, signal-to-noise ratio, depth penetration, portability, and cost. To help close these gaps, researchers at the Johns Hopkins University Applied Physics Laboratory (APL) are exploring optical techniques that record correlates of neural activity through either hemodynamic signatures or neural tissue motion as represented by the fast optical signal. Although these two signatures differ in terms of spatiotemporal resolution and depth at which the neural activity is recorded, they provide a path to realizing a portable, low-cost, high-performance brain–computer interface. If successful, this work will help usher in a new era of computing at the speed of thought.
Offshore observations at modern ocean-margin subduction zones (OMSZs) reveal that bodies of accreted material are commonly volumetrically small or missing, that crustal thinning and subsidence (3-5 ...km) has occurred, and that most trench axes lie close (5-30 km) to the seaward tapering edge of coastal basement rock. Onshore mapping commonly documents missing or only narrow terranes of former forearc rock and the inboard migration of the arc magmatic front. These observations are evidence that subduction is accompanied by the removal of sediment and crustal material from the submerged forearc by the kindred tectonic processes, respectively, of sediment subduction and subduction erosion. Subduction erosion truncates the margin (migrates the trench inboard) at ∼2.5 km/Ma. Onshore observations at ancient crust-suturing subduction zones (CSSZs) imply that collisional suturing is accompanied by sediment subduction and truncation of both upper and lower plates. During a protracted period of suturing (20-50 million years), a 100-200 km wide (or wider) band of the seaward edge of each plate can be removed subductively. Truncation of the upper plate is effected by subduction erosion, and that of the lower plate by the necking and break-off of its subducted edge. The average linear rate of crustal loss for each plate is estimated at ∼1.5 km/Ma, or ∼3 km/Ma combined. Because significant crustal loss occurs before and during tectonic fusing of colliding crustal blocks, structures and rock bodies that might be expected to record a former OMSZ and the formation of a CSSZ may be absent, unimpressively small, or preserved only as exhumed masses of once deeply subducted material.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Detroit Seamount, one of the northernmost seamounts of the Hawaiian‐Emperor seamount chain, was formed at ca. 76 Ma. New seismic data suggest renewed volcanism as late as 25 m.y. after initial ...seamount formation. We use high‐resolution single‐channel seismic (SCS) data acquired over the summit of Detroit Seamount in 2001 on Ocean Drilling Program (ODP) Leg 197, supplemented by older SCS data acquired as part of the GLORIA mapping program of the U.S. Geological Survey, to characterize the seismic stratigraphy of Detroit Seamount. Volcanic edifices occur on the summit of the seamount and are older than the oldest beds of the Meiji drift (early Oligocene: ca. 34 Ma). On the basis of ash layers in ODP drill holes, we suggest the edifices were active throughout much of the Eocene (ca. 52–34 Ma), with activity possibly extending into the early Oligocene (<34 Ma). Hence the age difference between the shield‐building lavas and the postshield cones on Detroit is far greater than the shield/postshield age differences observed on the Hawaiian Islands, suggesting that renewed volcanic activity and tectonic collapse may be possible on any of the Hawaiian Islands. We confirm earlier assertions that the thick sediment cap, Oligocene and younger in age, was deposited by an ocean‐bottom current with a southeastward flow direction, along the northeast facing flank of the Emperor Seamount chain. This sediment cap, the Meiji drift, was deposited by a lower‐velocity current than many other sediment drifts. A low‐angle normal fault, dipping ∼19°, suggests topographic collapse of Detroit seamount sometime during the Eocene or late Cretaceous.
Along the 450-km-long stretch of the Aleutian volcanic arc from Great Sitkin to Kiska Islands, edifice failure and submarine debris-avalanche deposition have occurred at seven of ten Quaternary ...volcanic centers. Reconnaissance geologic studies have identified subaerial evidence for large-scale prehistoric collapse events at five of the centers (Great Sitkin, Kanaga, Tanaga, Gareloi, and Segula). Side-scan sonar data collected in the 1980s by GLORIA surveys reveal a hummocky seafloor fabric north of several islands, notably Great Sitkin, Kanaga, Bobrof, Gareloi, Segula, and Kiska, suggestive of landslide debris. Simrad EM300 multibeam sonar data, acquired in 2005, show that these areas consist of discrete large blocks strewn across the seafloor, supporting the landslide interpretation from the GLORIA data. A debris-avalanche deposit north of Kiska Island (177.6° E, 52.1° N) was fully mapped by EM300 multibeam revealing a hummocky surface that extends 40 km from the north flank of the volcano and covers an area of ∼
380 km
2. A 24-channel seismic reflection profile across the longitudinal axis of the deposit reveals a several hundred-meter-thick chaotic unit that appears to have incised into well-bedded sediment, with only a few tens of meters of surface relief.
Edifice failures include thin-skinned, narrow, Stromboli-style collapse as well as Bezymianny-style collapse accompanied by an explosive eruption, but many of the events appear to have been deep-seated, removing much of an edifice and depositing huge amounts of debris on the sea floor. Based on the absence of large pyroclastic sheets on the islands, this latter type of collapse was not accompanied by large eruptions, and may have been driven by gravity failure instead of magmatic injection. Young volcanoes in the central and western portions of the arc (177° E to 175° W) are located atop the northern edge of the ∼
4000-m-high Aleutian ridge. The position of the Quaternary stratocones relative to the edge of the Aleutian ridge appears to strongly control their likelihood for, and direction of, past collapse. The ridge's steep drop to the north greatly increases potential runout length for slides that originate at the island chain.
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