Structural basis of mitochondrial receptor binding and constriction by DRP1.

Mitochondrial inheritance, genome maintenance and metabolic adaptation depend on organelle fission by dynamin-related protein 1 (DRP1) and its mitochondrial receptors. DRP1 receptors include the paralogues mitochondrial dynamics proteins of 49 and 51 kDa (MID49 and MID51) and mitochondrial fission factor (MFF); however, the mechanisms by which these proteins recruit and regulate DRP1 are unknown. Here we present a cryo-electron microscopy structure of full-length human DRP1 co-assembled with MID49 and an analysis of structure- and disease-based mutations. We report that GTP induces a marked elongation and rotation of the GTPase domain, bundle-signalling element and connecting hinge loops of DRP1. In this conformation, a network of multivalent interactions promotes the polymerization of a linear DRP1 filament with MID49 or MID51. After co-assembly, GTP hydrolysis and exchange lead to MID receptor dissociation, filament shortening and curling of DRP1 oligomers into constricted and closed rings. Together, these views of full-length, receptor- and nucleotide-bound conformations reveal how DRP1 performs mechanical work through nucleotide-driven allostery

A new customised placental weight standard redefines the relationship between maternal obesity and extremes of placental size and is more closely associated with pregnancy complications than an existing population standard

JW and GH were funded by the Scottish Government’s Rural and Environmental Science and Analytical Services Division (RESAS) who had no input into the content or preparation of the manuscript.Peer reviewedPostprin

Multi-time delay, multi-point Linear Stochastic Estimation of a cavity shear layer velocity from wall-pressure measurements

Multi-time-delay Linear Stochastic Estimation (MTD-LSE) technique is thoroughly described, focusing on its fundamental properties and potentialities. In the multi-time-delay ap- proach, the estimate of the temporal evolution of the velocity at a given location in the flow field is obtained from multiple past samples of the unconditional sources. The technique is applied to estimate the velocity in a cavity shear layer flow, based on wall-pressure measurements from multiple sensor

Design of Allosteric Stimulators of the Hsp90 ATPase as New Anticancer Leads

Allosteric compounds that stimulate Hsp90 adenosine triphosphatase (ATPase) activity were rationally designed, showing anticancer potencies in the low micromolar to nanomolar range. In parallel, the mode of action of these compounds was clarified and a quantitative model that links the dynamic ligand-protein cross-talk to observed cellular and in vitro activities was developed. The results support the potential of using dynamics-based approaches to develop original mechanism-based cancer therapeutics

Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin.

Gene silencing by heterochromatin is proposed to occur in part as a result of the ability of heterochromatin protein 1 (HP1) proteins to spread across large regions of the genome, compact the underlying chromatin and recruit diverse ligands. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation-driven phase separation can be promoted or reversed by specific HP1α ligands. Known components of heterochromatin such as nucleosomes and DNA preferentially partition into the HP1α droplets, but molecules such as the transcription factor TFIIB show no preference. Using a single-molecule DNA curtain assay, we find that both unmodified and phosphorylated HP1α induce rapid compaction of DNA strands into puncta, although with different characteristics. We show by direct protein delivery into mammalian cells that an HP1α mutant incapable of phase separation in vitro forms smaller and fewer nuclear puncta than phosphorylated HP1α. These findings suggest that heterochromatin-mediated gene silencing may occur in part through sequestration of compacted chromatin in phase-separated HP1 droplets, which are dissolved or formed by specific ligands on the basis of nuclear context

Teichm\"uller's problem in space

Quasiconformal homeomorphisms of the whole space Rn, onto itself normalized at one or two points are studied. In particular, the stability theory, the case when the maximal dilatation tends to 1, is in the focus. Our main result provides a spatial analogue of a classical result due to Teichm\"uller. Unlike Teichm\"uller's result, our bounds are explicit. Explicit bounds are based on two sharp well-known distortion results: the quasiconformal Schwarz lemma and the bound for linear dilatation. Moreover, Bernoulli type inequalities and asymptotically sharp bounds for special functions involving complete elliptic integrals are applied to simplify the computations. Finally, we discuss the behavior of the quasihyperbolic metric under quasiconformal maps and prove a sharp result for quasiconformal maps of R^n \ {0} onto itself.Comment: 25 pages, 2 figure

Ferromagnetic effect and spin assignment for the 390 keV state in 62Cu

The 390 keV isomeric state of 62Cu is assigned as Jπ = 4+. The magnetic hyperfine interaction has been observed in the 60Ni(α, pnγ) 62Cu reaction and the deduced Larmor period is consistent with known values of g and the hyperfine field of Cu in Ni

Modular Equations and Distortion Functions

Modular equations occur in number theory, but it is less known that such equations also occur in the study of deformation properties of quasiconformal mappings. The authors study two important plane quasiconformal distortion functions, obtaining monotonicity and convexity properties, and finding sharp bounds for them. Applications are provided that relate to the quasiconformal Schwarz Lemma and to Schottky's Theorem. These results also yield new bounds for singular values of complete elliptic integrals.Comment: 23 page

A PRELIMINARY INVESTIGATION TO THE POSSIBLE IMPACT OF EL NINO/SOUTHERN OSCILLATION (ENSO) PHENOMENA ON THE CLIMATE OF TRINIDAD AND TOBAGO USING REMOTELY SENSED DATA

Abstract Trinidad and Tobago like most other small developing island states is quite vulnerable to changes in Climate and Sea Surface Temperature (SST). Climate changes can affect the rainfall regimes, air temperature, soil moisture budgets, water resources and arable land usage. While changes in air and sea surface temperature can adversely affect coral reefs, mangroves, sea grass bed communities and fishery populations that depend on them for habitat and breeding grounds. Analysis of the temporal and spatial changes of SST over the years is an important way of understanding the present variability in the climate. This will then allow for an improved assessment of the susceptibility, vulnerability and risk that both humans and natural ecosystems may face because of the changes in the coupling interaction of the various components of the Earth's environmental system. However, decision-making, management and developing environmental policies in this regard is seriously compromised due information poverty, i.e. the lack of data of effective and reliable information base. This paper advances a methodology to endure information poverty and to obtain and analyse the SST patterns utilising it as a proxy for determining the climate variability of Trinidad and Tobago. The methodology is based on obtaining, using and analysing available remotely sensed SST from the National Oceanographic and Atmospheric Agency (NOAA) via the Internet. As well as using available rainfall data. In the case of Trinidad and Tobago, the SST and rainfall data was obtained for the last 16 years. Mean monthly values of SST and rainfall for the period 1986-1999 were then derived. The results indicate that variability in the climate is occurring. Furthermore, it shows that during the El Niño years 1986-87 and 1997-98, the SST were at a maximum while the rainfall fell to minimum. The preliminary results indicated the possibility of developing statistical associations between SST and land precipitation as well as the association between the SST-land precipitation pattern and external events such as the El Niño Southern Oscillation (ENSO) phenomenon. These ideas in turn can lead to investigating the association between the variability in SST and land precipitation on water resources and land use patterns that might lead to the possible prediction of the land precipitation patterns based on SST analysis