Tri-snRNP-associated proteins interact with subunits of the TRAMP and nuclear exosome complexes, linking RNA decay and pre-mRNA splicing

Nuclear RNA decay factors are involved in many different pathways including rRNA processing, snRNA and snoRNA biogenesis, pre-mRNA processing, and the rapid decay of cryptic intergenic transcripts. In contrast to its yeast counterpart, the mammalian nuclear decay machinery is largely uncharacterized. Here we report interactions of several putative components of the human nuclear RNA decay machinery, including the TRAMP complex protein Mtr4 and the nuclear exosome constituents PM/Scl-100 and PM/Scl-75, with components of the U4/U6.U5 tri-snRNP complex required for pre-mRNA splicing. The tri-snRNP component Prp31 interacts indirectly with Mtr4 and PM/Scl-100 in a manner that is dependent on the phosphorylation sites in the middle of the protein, while Prp3 and Prp4 interact with the nuclear decay complex independent of Prp31. Together our results suggest recruitment of the nuclear decay machinery to the spliceosome to ensure production of properly spliced mRNA

On the Explanation of the Paramagnetic Meissner Effect in Superconductor/Ferromagnet Heterostructures

An increase of the magnetic moment in superconductor/ferromagnet (S/F) bilayers V(40nm)/F [F$=$Fe(1,3nm), Co(3nm), Ni(3nm)] was observed using SQUID magnetometry upon cooling below the superconducting transition temperature Tc in magnetic fields of 10 Oe to 50 Oe applied parallel to the sample surface. A similar increase, often called the paramagnetic Meissner effect (PME), was observed before in various superconductors and superconductor/ferromagnet systems. To explain the PME effect in the presented S/F bilayers a model based on a row of vortices located at the S/F interface is proposed. According to the model the magnetic moment induced below Tc consists of the paramagnetic contribution of the vortex cores and the diamagnetic contribution of the vortex-free region of the S layer. Since the thickness of the S layer is found to be 3-4 times less than the magnetic field penetration depth, this latter diamagnetic contribution is negligible. The model correctly accounts for the sign, the approximate magnitude and the field dependence of the paramagnetic and the Meissner contributions of the induced magnetic moment upon passing the superconducting transition of a ferromagnet/superconductor bilayer

Volume-rendered optical coherence tomography angiography during ocular interventions: Advocating for noninvasive intraoperative retinal perfusion monitoring.

We aimed to test for feasibility of volume-rendered optical coherence tomography angiography (OCTA) as a novel method for assessing/quantifying retinal vasculature during ocular procedures and to explore the potential for intraoperative use. Thirty patients undergoing periocular anaesthesia were enrolled, since published evidence suggests a reduction in ocular blood flow. Retinal perfusion was monitored based on planar OCTA image-derived data provided by a standard quantification algorithm and postprocessed/volume-rendered OCTA data using a custom software script. Overall, imaging procedures were successful, yet imaging artifacts occurred frequently. In interventional eyes, perfusion parameters decreased during anaesthesia. Planar image-derived and volume rendering-derived parameters were correlated. No correlation was found between perfusion parameters and a motion artifact score developed for this study, yet all perfusion parameters correlated with signal strength as displayed by the device. Concluding, volume-rendered OCTA allows for noninvasive three-dimensional retinal vasculature assessment/quantification in challenging surgical settings and appears generally feasible for intraoperative use

Interdependence between training and magnetization reversal in granular Co-CoO exchange bias systems

The interdependence between training and magnetization reversal in granular Co-CoO exchange bias (EB) systems prepared byOion implantation inCo thin films is demonstrated by polarized neutron reflectometry. While high-fluence O-implanted thin films show reduced relative training values and no asymmetry in magnetization reversal (all reversals take place by domain wall nucleation and motion), low-fluence O ion implantation results in an increased relative training and a magnetization reversal asymmetry between the first descending and the first ascending branches. Whereas the untrained decreasing field reversal occurs mainly by domain wall nucleation and motion, traces of a domain rotation contribution are evidenced in the increasing field reversal. This is explained by the evolution of the CoO structure and the contribution of the out-of-plane magnetization with ion implantation. The amount of incorporated O, which determines the threshold between both behaviors, is around 20 at.%. This reveals that the interdependence between training and magnetization reversal is insensitive to the morphology of the constituents (i.e., granular or layered), indicating that this is an intrinsic EB effect, which can be conveniently tailored by the interplay between the intrinsic properties of the investigated materials and ion implantation

The origin of life: chemical evolution of a metabolic system in a mineral honeycomb?

For the RNA-world hypothesis to be ecologically feasible, selection mechanisms acting on replicator communities need to be invoked and the corresponding scenarios of molecular evolution specified. Complementing our previous models of chemical evolution on mineral surfaces, in which selection was the consequence of the limited mobility of macromolecules attached to the surface, here we offer an alternative realization of prebiotic group-level selection: the physical encapsulation of local replicator communities into the pores of the mineral substrate. Based on cellular automaton simulations we argue that the effect of group selection in a mineral honeycomb could have been efficient enough to keep prebiotic ribozymes of different specificities and replication rates coexistent, and their metabolic cooperation protected from extensive molecular parasitism. We suggest that mutants of the mild parasites persistent in the metabolic system can acquire useful functions such as replicase activity or the production of membrane components, thus opening the way for the evolution of the first autonomous protocells on Earth

Utilization of a deoxynucleoside diphosphate substrate by HIV reverse transcriptase

Background: Deoxynucleoside triphosphates (dNTPs) are the normal substrates for DNA sysnthesis is catalyzed by polymerases such as HIV-1 reverse transcriptase (RT). However, substantial amounts of deoxynucleoside diphosphates (dNDPs) are also present in the cell. Use of dNDPs in HIV-1 DNA sysnthesis could have significant implications for the efficacy of nucleoside RT inhibitors such as AZT which are first line therapeutics fro treatment of HIV infection. Our earlier work on HIV-1 reverse transcriptase (RT) suggested that the interaction between the γ phosphate of the incoming dNTP and RT residue K65 in the active site is not essential for dNTP insertion, implying that this polymerase may be able to insert dNPs in addition to dNTPs. Methodology/Principal Findings: We examined the ability of recombinant wild type (wt) and mutant RTs with substitutions at residue K65 to utilize a dNDP substrate in primer extension reactions. We found that wild type HIV-1 RT indeed catalyzes incorporation of dNDP substrates whereas RT with mutations of residue K645 were unable to catalyze this reaction. Wild type HIV-1 RT also catalyzed the reverse reaction, inorganic phosphate-dependent phosphorolysis. Nucleotide-mediated phosphorolytic removal of chain-terminating 3′-terminal nucleoside inhibitors such as AZT forms the basis of HIV-1 resistance to such drugs, and this removal is enhanced by thymidine analog mutations (TAMs). We found that both wt and TAM-containing RTs were able to catalyze Pi-mediated phosphorolysis of 3′-terminal AZT at physiological levels of Pi with an efficacy similar to that for ATP-dependent AZT-excision. Conclusion: We have identified two new catalytic function of HIV-1 RT, the use of dNDPs as substrates for DNA synthesis, and the use of Pi as substrate for phosphorolytic removal of primer 3′-terminal nucleotides. The ability to insert dNDPs has been documented for only one other DNA polymerase The RB69 DNA polymerase and the reverse reaction employing inorganic phosphate has not been documented for any DNA polymerase. Importantly, our results show that Pi-mediated phosphorolysis can contribute to AZT resistance and indicates that factors that influence HIV resistance to AZT are more complex than previously appreciated. © 2008 Garforth et al