A Paleomagnetic Inspection of the Paleocene-Eocene Thermal Maximum (PETM) in the Southern Pyrenees

Magnetic properties of rocks can be useful for determining paleoenvironmental changes. A dramatic climate change that occurred in the Paleocene-Eocene Thermal Maximum (PETM) modified the environment and, hence, the magnetic properties recorded in the sediments. New paleomagnetic data from marine records of the PETM in the Southern Pyrenean zone displays a variation of the magnetic parameters in four different sections. The magnetic signal reveals a positive excursion of magnetic values starting before the onset of the marly interval of La Faja de las Flores Mb (beginning of the PETM record, Ilerdian) in the Carriata section with a maximum value in the marly interval. A similar magnetic signal is observed in the Bujaruelo section (similar to 10 km south of Carriata at PETM times) that is related directly to the marly interval of Faja de las Flores Mb. However, towards the south, the PETM interval does not appear in the sedimentary record; therefore, in the southern Gallisue section, no magnetic excursion occurs. In the southernmost-studied Entremon section, a positive magnetic excursion occurs in a thin marly interval unrelated to the PETM, and in two lower intervals of the column. All sections were later subjected to deformation during the pyrean orogeny and the three northernmost sections in the regional cleavage front, where pressure solution and remagnetizations have been described. A post-folding remagnetization component is found in the three northern sections

The Hexamer Structure of the Rift Valley Fever Virus Nucleoprotein Suggests a Mechanism for its Assembly into Ribonucleoprotein Complexes

Rift Valley fever virus (RVFV), a Phlebovirus with a genome consisting of three single-stranded RNA segments, is spread by infected mosquitoes and causes large viral outbreaks in Africa. RVFV encodes a nucleoprotein (N) that encapsidates the viral RNA. The N protein is the major component of the ribonucleoprotein complex and is also required for genomic RNA replication and transcription by the viral polymerase. Here we present the 1.6 Å crystal structure of the RVFV N protein in hexameric form. The ring-shaped hexamers form a functional RNA binding site, as assessed by mutagenesis experiments. Electron microscopy (EM) demonstrates that N in complex with RNA also forms rings in solution, and a single-particle EM reconstruction of a hexameric N-RNA complex is consistent with the crystallographic N hexamers. The ring-like organization of the hexamers in the crystal is stabilized by circular interactions of the N terminus of RVFV N, which forms an extended arm that binds to a hydrophobic pocket in the core domain of an adjacent subunit. The conformation of the N-terminal arm differs from that seen in a previous crystal structure of RVFV, in which it was bound to the hydrophobic pocket in its own core domain. The switch from an intra- to an inter-molecular interaction mode of the N-terminal arm may be a general principle that underlies multimerization and RNA encapsidation by N proteins from Bunyaviridae. Furthermore, slight structural adjustments of the N-terminal arm would allow RVFV N to form smaller or larger ring-shaped oligomers and potentially even a multimer with a super-helical subunit arrangement. Thus, the interaction mode between subunits seen in the crystal structure would allow the formation of filamentous ribonucleocapsids in vivo. Both the RNA binding cleft and the multimerization site of the N protein are promising targets for the development of antiviral drugs

Modelling the long-term dynamics of the energy transition accounting for socioeconomic behaviour and biophysical constraints: overview of the Wiliam Energy Module

WILIAM (Within Limit Integrated Assessment Model) is a global multiregional IAM that combines economic, social, demographic, environmental, energy and material related aspects into one system dynamics model. It aims to provide stakeholders with an open source, welldocumented model to assess the feasibility, effectiveness, costs and impacts of different sustainability policy options. The adequate representation of energy production is key to assess future sustainability pathways. The main function of the developed energy module is to estimate the primary energy requirements and related GHG emissions for satisfying the economic demand. This goal was achieved by 7 major sub-modules: (1) End-use: translates the economic demand into final energy demand through a hybrid approach combining bottom-up with energy intensities for different sectors. (2) Energy transformation: maps the entire energy conversion chain from final to primary energy, including intermediary energy commodities and an allocation function for power plant utilization. (3) Energy capacity: keeps track of the current power plant capacity stock, decommissioning of expired capacities, as well as the build-up of new capacities. An allocation function for choosing the suitable technology types for new capacities stands at the core of this sub-module. (4) Computation of the EROI of green technologies (5) Variability and storage: keeps track of sub-annual time scale effects on annual energy balances depending on the current power system setup (DSM, Storage, sector coupling). (6) Consideration of techno-sustainable potentials of RES considering geographical, resource and Energy Return on Energy Investment (EROI) constraints. (7) Computation of the energy-related GHG emissions

Mice with Mutation in Dynein Heavy Chain 1 Do Not Share the Same Tau Expression Pattern with Mice with SOD1-Related Motor Neuron Disease

Due to controversy about the involvement of Dync1h1 mutation in pathogenesis of motor neuron disease, we investigated expression of tau protein in transgenic hybrid mice with Dync1h1 (so-called Cra1/+), SOD1G93A (SOD1/+), double (Cra1/SOD1) mutations and wild-type controls. Total tau-mRNA and isoforms 0, 1 and 2 N expression was studied in frontal cortex, hippocampus, spinal cord and cerebellum of presymptomatic and symptomatic animals (age 70, 140 and 365 days). The most significant differences were found in brain cortex and cerebellum, but not in hippocampus and spinal cord. There were less changes in Cra1/SOD1 double heterozygotes compared to mice harboring single mutations. The differences in total tau expression and in profile of its isoforms between Cra1/+ and SOD1/+ transgenics indicate a distinct pathogenic entity of these two conditions

A Structural Model of the Pore-Forming Region of the Skeletal Muscle Ryanodine Receptor (RyR1)

Ryanodine receptors (RyRs) are ion channels that regulate muscle contraction by releasing calcium ions from intracellular stores into the cytoplasm. Mutations in skeletal muscle RyR (RyR1) give rise to congenital diseases such as central core disease. The absence of high-resolution structures of RyR1 has limited our understanding of channel function and disease mechanisms at the molecular level. Here, we report a structural model of the pore-forming region of RyR1. Molecular dynamics simulations show high ion binding to putative pore residues D4899, E4900, D4938, and D4945, which are experimentally known to be critical for channel conductance and selectivity. We also observe preferential localization of Ca2+ over K+ in the selectivity filter of RyR1. Simulations of RyR1-D4899Q mutant show a loss of preference to Ca2+ in the selectivity filter as seen experimentally. Electrophysiological experiments on a central core disease mutant, RyR1-G4898R, show constitutively open channels that conduct K+ but not Ca2+. Our simulations with G4898R likewise show a decrease in the preference of Ca2+ over K+ in the selectivity filter. Together, the computational and experimental results shed light on ion conductance and selectivity of RyR1 at an atomistic level

Structural insights into Ca2+-activated long-range allosteric channel gating of RyR1

Ryanodine receptors (RyRs) are a class of giant ion channels with molecular mass over 2.2 mega-Daltons. These channels mediate calcium signaling in a variety of cells. Since more than 80% of the RyR protein is folded into the cytoplasmic assembly and the remaining residues form the transmembrane domain, it has been hypothesized that the activation and regulation of RyR channels occur through an as yet uncharacterized long-range allosteric mechanism. Here we report the characterization of a Ca2+-activated open-state RyR1 structure by cryo-electron microscopy. The structure has an overall resolution of 4.9 angstrom and a resolution of 4.2 angstrom for the core region. In comparison with the previously determined apo/closed-state structure, we observed long-range allosteric gating of the channel upon Ca2+ activation. In-depth structural analyses elucidated a novel channel-gating mechanism and a novel ion selectivity mechanism of RyR1. Our work not only provides structural insights into the molecular mechanisms of channel gating and regulation of RyRs, but also sheds light on structural basis for channel-gating and ion selectivity mechanisms for the six-transmembrane-helix cation channel family.Strategic Priority Research Program of Chinese Academy of Sciences [XDB08030202]; National Basic Research Program (973 Program); Ministry of Science & Technology of China [2012CB917200, 2014CB910700]; National Natural Science Foundation of China [31270768]; Ministry of Education of China (111 Program China)SCI(E)PubMed中国科技核心期刊(ISTIC)[email protected]; [email protected]

Effect of static stretching of quadriceps and hamstring muscles on knee joint position sense

Objectives: To evaluate if a stretch regimen consisting of three 30 second stretches would alter joint position sense (JPS). Methods: A blinded, randomised, cross over design with a washout time of 24 hours was used with 20 healthy volunteers. JPS was estimated from the ability to reproduce the same position in one knee (target versus estimated angle) expressed as the difference between target and estimated angle (constant error, CE). Measurements were repeated three times in a sitting and a prone position on the dominant leg measured before and immediately after the static stretch. The static stretch consisted of a 30 second stretch followed by a 30 second pause, repeated three times. Results: At baseline, the mean (SD) CE was –2.71 (3.57)° in the sitting position. No difference (p = 0.99) in CE between stretching and control was observed (0.00; 95% confidence interval –0.98 to 0.99). At baseline, the CE was –3.28 (4.81)° in the prone position. No difference (p = 0.89) in CE between stretching and control was observed (0.12; 95% confidence interval –1.52 to 1.76). Conclusion: A static stretch regimen had no effect on JPS in healthy volunteers