Massive open online courses (MOOCs) have generated enthusiasm, excitement, and hype worldwide and recently increasing skepticism. They are being broadly discussed in the major news media (and to a ...smaller extent in academic circles). Rapidly increasing numbers of MOOC providers, MOOC courses and articles, discussion groups, and blogs discussing MOOCs are indicators of the involvement of many stakeholders. Most of these analyses and developments are based on economic perspectives (such as scalability, productivity, and being free) and technology perspectives (including platforms supporting large number of students in online environments, enrichment components such as forums, peer-to-peer learning support, and automatic grading). Few contributions analyze MOOCs from a learning science perspective and put them into a larger context with other approaches to learning and education. This commentary explores challenges derived from the perspective to conceptualize MOOCs as being one component in a rich landscape of learning.
Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric ...growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-β1 and pro-BMP-9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein.
The Mg/Ca of planktic foraminifera Globigerinoides ruber (white) is a widely applied proxy for tropical and sub-tropical sea-surface temperature. The accuracy with which temperature can be ...reconstructed depends on how accurately relationships between Mg/Ca and temperature and the multiple secondary controls on Mg/Ca are known; however, these relationships remain poorly quantified under oceanic conditions. Here, we present new calibrations based on 440 sediment trap/plankton tow samples from the Atlantic, Pacific and Indian Oceans, including 130 new samples from the Bay of Bengal/Arabian Sea and the tropical Atlantic Ocean. Our results indicate temperature, salinity and the carbonate system all significantly influence Mg/Ca in G. ruber (white). We propose two calibration models: The first model assumes pH is the controlling carbonate system parameter. In this model, Mg/Ca has a temperature sensitivity of 6.0±0.8%/°C (2σ), a salinity sensitivity of 3.3±2.2%/PSU and a pH sensitivity of −8.3±7.7%/0.1 pH units; The second model assumes carbonate ion concentration (CO32−) is the controlling carbonate system parameter. In this model, Mg/Ca has a temperature sensitivity of 6.7±0.8%/°C, a salinity sensitivity of 5.0±3.0%/PSU and a CO32− sensitivity of −0.24±0.11%/μmol kg−1. In both models, the temperature sensitivity is significantly lower than the widely-applied sensitivity of 9.0±0.6%/°C. Application of our new calibrations to down-core data from the Last Glacial Maximum, considering whole ocean changes in salinity and carbonate chemistry, indicate a cooling of 2.4±1.6°C in the tropical oceans if pH is the controlling parameter and 1.5±1.4°C if CO32− is the controlling parameter.
•New Mg/Ca calibration based on 440 sediment trap/plankton tow samples.•The sensitivity of Mg/Ca to temperature is ∼6/°C.•The sensitivity of Mg/Ca to salinity is ∼3%.•The carbonate system significantly influences Mg/Ca.
Aquaporins are membrane channels that facilitate the flow of water across biological membranes. Two conserved regions are central for selective function: the dual asparagine-proline-alanine (NPA) ...aquaporin signature motif and the aromatic and arginine selectivity filter (SF). Here, we present the crystal structure of a yeast aquaporin at 0.88 angstrom resolution. We visualize the H-bond donor interactions of the NPA motifs asparagine residues to passing water molecules; observe a polarized water-water H-bond configuration within the channel; assign the tautomeric states of the SF histidine and arginine residues; and observe four SF water positions too closely spaced to be simultaneously occupied. Strongly correlated movements break the connectivity of SF waters to other water molecules within the channel and prevent proton transport via a Grotthuss mechanism.
We analyzed size-specific dry mass, sinking velocity, and apparent diffusivity in field-sampled marine snow, laboratory-made aggregates formed by diatoms or coccolithophorids, and small and large ...zooplankton fecal pellets with naturally varying content of ballast materials. Apparent diffusivity was measured directly inside aggregates and large (millimeter-long) fecal pellets using microsensors. Large fecal pellets, collected in the coastal upwelling off Cape Blanc, Mauritania, showed the highest volume-specific dry mass and sinking velocities because of a high content of opal, carbonate, and lithogenic material (mostly Saharan dust), which together comprised ~80% of the dry mass. The average solid matter density within these large fecal pellets was 1.7 g cm⁻³, whereas their excess density was 0.25 ± 0.07 g cm⁻³. Volume-specific dry mass of all sources of aggregates and fecal pellets ranged from 3.8 to 960 micrograms mm⁻³, and average sinking velocities varied between 51 and 732 m d⁻¹. Porosity was >0.43 and >0.96 within fecal pellets and phytoplankton-derived aggregates, respectively. Averaged values of apparent diffusivity of gases within large fecal pellets and aggregates were 0.74 and 0.95 times that of the free diffusion coefficient in sea water, respectively. Ballast increases sinking velocity and, thus, also potential O2 fluxes to sedimenting aggregates and fecal pellets. Hence, ballast minerals limit the residence time of aggregates in the water column by increasing sinking velocity, but apparent diffusivity and potential oxygen supply within aggregates are high, whereby a large fraction of labile organic carbon can be respired during sedimentation.
Lithogenic material such as Saharan dust can be incorporated into organic aggregates and act as ballast, potentially enhancing the marine carbon export via increased sinking velocities of aggregates. ...We studied the ballasting effects of Saharan dust on the aggregate dynamics in the upwelling region off Cape Blanc (Mauritania). Aggregate formation from a natural plankton community exposed to Saharan dust deposition resulted in higher abundance of aggregates with higher sinking velocities compared to aggregate formation with low dust. This higher aggregate abundance and sinking velocities potentially increased the carbon export 10-fold when the aggregates were ballasted by Saharan dust. After aggregate formation in the surface waters, subsequent sinking through suspended Saharan dust minerals had no influence on aggregate sizes, abundance, and sinking velocities. We found that aggregates formed in the surface ocean off Mauritania were already heavily ballasted with lithogenic material and could therefore not scavenge any additional minerals during their descent. This suggests that carbon export to the deep ocean in regions with high dust deposition is strongly controlled by dust input to the surface ocean while suspended dust particles in deeper water layers do not significantly interact with sinking aggregates.
This paper presents a new physical compact model for interface state creation due to hot-carrier degradation in advanced SiGe heterojunction bipolar transistors (HBTs). An analytical model for trap ...density is developed through an accurate solution of the rate equation describing generation and annihilation of interface traps. The analytical aging law has been derived and implemented in terms of base recombination current parameters in HiCuM compact model and its accuracy has been validated against results from long-term aging tests performed close to the safe-operating areas of various HBT technologies. The model implementation uses a single additional node, alike previous implementations, thereby preserving its simplicity, yet improving the accuracy and the physical basis of degradation.
Myostatin, a key regulator of muscle mass in vertebrates, is biosynthesised as a latent precursor in muscle and is activated by sequential proteolysis of the pro‐domain. To investigate the molecular ...mechanism by which pro‐myostatin remains latent, we have determined the structure of unprocessed pro‐myostatin and analysed the properties of the protein in its different forms. Crystal structures and SAXS analyses show that pro‐myostatin adopts an open, V‐shaped structure with a domain‐swapped arrangement. The pro‐mature complex, after cleavage of the furin site, has significantly reduced activity compared with the mature growth factor and persists as a stable complex that is resistant to the natural antagonist follistatin. The latency appears to be conferred by a number of distinct features that collectively stabilise the interaction of the pro‐domains with the mature growth factor, enabling a regulated stepwise activation process, distinct from the prototypical pro‐TGF‐β1. These results provide a basis for understanding the effect of missense mutations in pro‐myostatin and pave the way for the design of novel myostatin inhibitors.
Synopsis
The structure of the precursor of the muscle mass regulator myostatin/GDF8 shows an open‐armed conformation, similar to pro‐activin A and distinct from pro‐TGF‐β1. An enhanced interface between prodomains and the mature growth factor allows pro‐myostatin to persist as a latent, antagonist resistant complex even after processing of the precursor by furin‐like proteases.
The crystal structure of unprocessed human pro‐myostatin was determined, and is shown to have an open‐armed, domain swapped architecture.
Following pro‐domain cleavage, pro‐myostatin persists as a stable non‐covalent complex and has significantly lower bioactivity than the mature growth factor.
Latency of the pro‐myostatin complex is achieved by an enhanced interface between pro‐ and mature domains.
The natural antagonist follistatin is unable to displace the prodomains of the latent myostatin complex.
The crystal structure of a myostatin/GDF8 precursor reveals an open‐armed conformation and provides insight into the sequential activation of this muscle mass regulator upon proteolytic cleavage.
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