CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1.

Na+-coupled acid-base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na+-coupled acid-base transporters are not available. The sodium-bicarbonate cotransporter NBCe1 functions in multiple organs and its mutations cause blindness, abnormal growth and blood chemistry, migraines, and impaired cognitive function. Here, we have determined the structure of the membrane domain dimer of human NBCe1 at 3.9 Å resolution by cryo electron microscopy. Our atomic model and functional mutagenesis revealed the ion accessibility pathway and the ion coordination site, the latter containing residues involved in human disease-causing mutations. We identified a small number of residues within the ion coordination site whose modification transformed NBCe1 into an anion exchanger. Our data suggest that symporters and exchangers utilize comparable transport machinery and that subtle differences in their substrate-binding regions have very significant effects on their transport mode

Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex.

The nuclear pore complex mediates nucleocytoplasmic transport in all eukaryotes and is among the largest cellular assemblies of proteins, collectively known as nucleoporins. Nucleoporins are organized into distinct subcomplexes. We optimized the isolation of a putative membrane-coating subcomplex of the nuclear pore complex, the heptameric Nup84 complex, and analyzed its structure by EM. Our data confirmed the previously reported 'Y' shape. We discerned additional structural details, including specific hinge regions at which the particle shows great flexibility. We determined the three-dimensional structures of two conformers, mapped the localization of two nucleoporins within the subcomplex and docked known crystal structures into the EM maps. The free ends of the Y-shaped particle are formed by beta-propellers; the connecting segments consist of alpha-solenoids. Notably, the same organizational principle is found in the clathrin triskelion, which may share a common evolutionary origin with the heptameric complex

Halo Coronal Mass Ejections during Solar Cycle 24: reconstruction of the global scenario and geoeffectiveness

In this study we present a statistical analysis of 53 fast Earth-directed halo CMEs observed by the SOHO/LASCO instrument during the period Jan. 2009-Sep. 2015, and we use this CME sample to test the capabilities of a Sun-to-Earth prediction scheme for CME geoeffectiveness. First, we investigate the CME association with other solar activity features by means of multi-instrument observations of the solar magnetic and plasma properties. Second, using coronagraphic images to derive the CME kinematical properties at 0.1 AU, we propagate the events to 1 AU by means of the WSA-ENLIL+Cone model. Simulation results at Earth are compared with in-situ observations at L1. By applying the pressure balance condition at the magnetopause and a solar wind-Kp index coupling function, we estimate the expected magnetospheric compression and geomagnetic activity level, and compare them with global data records. The analysis indicates that 82% of the CMEs arrived at Earth in the next 4 days. Almost the totality of them compressed the magnetopause below geosynchronous orbits and triggered a geomagnetic storm. Complex sunspot-rich active regions associated with energetic flares result the most favourable configurations from which geoeffective CMEs originate. The analysis of related SEP events shows that 74% of the CMEs associated with major SEPs were geoeffective. Moreover, the SEP production is enhanced in the case of fast and interacting CMEs. In this work we present a first attempt at applying a Sun-to-Earth geoeffectiveness prediction scheme - based on 3D simulations and solar wind-geomagnetic activity coupling functions - to a statistical set of potentially geoeffective halo CMEs. The results of the prediction scheme are in good agreement with geomagnetic activity data records, although further studies performing a fine-tuning of such scheme are needed.Comment: Accepted for publication in the Journal of Space Weather and Space Climate (SWSC

Structure of the substrate-engaged SecA-SecY protein translocation machine.

The Sec61/SecY channel allows the translocation of many proteins across the eukaryotic endoplasmic reticulum membrane or the prokaryotic plasma membrane. In bacteria, most secretory proteins are transported post-translationally through the SecY channel by the SecA ATPase. How a polypeptide is moved through the SecA-SecY complex is poorly understood, as structural information is lacking. Here, we report an electron cryo-microscopy (cryo-EM) structure of a translocating SecA-SecY complex in a lipid environment. The translocating polypeptide chain can be traced through both SecA and SecY. In the captured transition state of ATP hydrolysis, SecAs two-helix finger is close to the polypeptide, while SecAs clamp interacts with the polypeptide in a sequence-independent manner by inducing a short β-strand. Taking into account previous biochemical and biophysical data, our structure is consistent with a model in which the two-helix finger and clamp cooperate during the ATPase cycle to move a polypeptide through the channel

Ono: an open platform for social robotics

In recent times, the focal point of research in robotics has shifted from industrial ro- bots toward robots that interact with humans in an intuitive and safe manner. This evolution has resulted in the subfield of social robotics, which pertains to robots that function in a human environment and that can communicate with humans in an int- uitive way, e.g. with facial expressions. Social robots have the potential to impact many different aspects of our lives, but one particularly promising application is the use of robots in therapy, such as the treatment of children with autism. Unfortunately, many of the existing social robots are neither suited for practical use in therapy nor for large scale studies, mainly because they are expensive, one-of-a-kind robots that are hard to modify to suit a specific need. We created Ono, a social robotics platform, to tackle these issues. Ono is composed entirely from off-the-shelf components and cheap materials, and can be built at a local FabLab at the fraction of the cost of other robots. Ono is also entirely open source and the modular design further encourages modification and reuse of parts of the platform