Structure of a sheared soft-disk fluid from a nonequilibrium potential

The distortion of structure of a simple, inverse-12, soft-disk fluid undergoing two-dimensional plane Couette flow was studied by nonequilibrium molecular dynamics (NEMD) simulation and by equilibrium Monte Carlo (MC) simulation with a nonequilibrium potential, under which the equilibrium structure of the fluid is that of the nonequilibrium fluid. Extension of the iterative predictor-corrector method of [Reatto Phys. Rev. A 33 3451 (1986)] was used to extract the nonequilibrium potential with the structure input from the NEMD simulation. Very good agreement for the structural properties and pressure tensor generated by the NEMD and MC simulation methods was found, thus providing the evidence that nonequilibrium liquid structure can be accurately reproduced via simple equilibrium simulations or theories using a properly chosen nonequilibrium potential. The method developed in the present study and numerical results presented here can be used to guide and test theoretical developments, providing them with the "experimental" results for the nonequilibrium potential.open2

Roundup 2.0: Enabling Comparative Genomics for over 1800 Genomes

Summary: Roundup is an online database of gene orthologs for over 1800 genomes, including 226 Eukaryota, 1447 Bacteria, 113 Archaea, and 21 Viruses. Orthologs are inferred using the Reciprocal Smallest Distance algorithm. Users may query Roundup for single-linkage clusters of orthologous genes based on any group of genomes. Annotated query results may be viewed in a variety of ways including as clusters of orthologs and as phylogenetic profiles. Genomic results may be downloaded in formats suitable for functional as well as phylogenetic analysis, including the recent OrthoXML standard. In addition, gene IDs can be retrieved using FASTA sequence search. All orthology results and source code are freely available

Probing ultrafast carrier dynamics and nonlinear absorption and refraction in core-shell silicon nanowires

We investigate the relaxation dynamics of photogenerated carriers in silicon nanowires consisting of a crystalline core and a surrounding amorphous shell, using femtosecond time-resolved differential reflectivity and transmission spectroscopy at photon energies of 3.15 eV and 1.57 eV. The complex behavior of the differential transmission and reflectivity transients is the mixed contributions from the crystalline core and the amorphous silicon on the nanowire surface and the substrate where competing effects of state filling and photoinduced absorption govern the carrier dynamics. Faster relaxation rates are observed on increasing the photo-generated carrier density. Independent experimental results on crystalline silicon-on-sapphire help us in separating the contributions from the carrier dynamics in crystalline core and the amorphous regions in the nanowire samples. Further, single beam z-scan nonlinear transmission experiments at 1.57 eV in both open and close aperture configurations yield two-photon absorption coefficient \$beta$ (~3 cm/GW) and nonlinear refraction coefficient \$gamma$ (-2.5x10^-4 cm2/GW).Comment: 6 pages, 6 figure

Transmission of mitochondrial DNA following assisted reproduction and nuclear transfer

Review of the articleMitochondria are the organelles responsible for producing the majority of a cell's ATP and also play an essential role in gamete maturation and embryo development. ATP production within the mitochondria is dependent on proteins encoded by both the nuclear and the mitochondrial genomes, therefore co-ordination between the two genomes is vital for cell survival. To assist with this co-ordination, cells normally contain only one type of mitochondrial DNA (mtDNA) termed homoplasmy. Occasionally, however, two or more types of mtDNA are present termed heteroplasmy. This can result from a combination of mutant and wild-type mtDNA molecules or from a combination of wild-type mtDNA variants. As heteroplasmy can result in mitochondrial disease, various mechanisms exist in the natural fertilization process to ensure the maternal-only transmission of mtDNA and the maintenance of homoplasmy in future generations. However, there is now an increasing use of invasive oocyte reconstruction protocols, which tend to bypass mechanisms for the maintenance of homoplasmy, potentially resulting in the transmission of either form of mtDNA heteroplasmy. Indeed, heteroplasmy caused by combinations of wild-type variants has been reported following cytoplasmic transfer (CT) in the human and following nuclear transfer (NT) in various animal species. Other techniques, such as germinal vesicle transfer and pronuclei transfer, have been proposed as methods of preventing transmission of mitochondrial diseases to future generations. However, resulting embryos and offspring may contain mtDNA heteroplasmy, which itself could result in mitochondrial disease. It is therefore essential that uniparental transmission of mtDNA is ensured before these techniques are used therapeutically

The clinical and therapeutic uses of MDM2 and PSMA and their potential interaction in aggressive cancers

Prostate-specific membrane antigen (PSMA) overexpression is observed in the neovasculature of solid tumors, but not in the vasculature of normal tissues. Increased PSMA expression is positively associated with tumor stage and grade, although its function in cancer remains unclear. Mouse double minute 2 (MDM2) is a negative regulator of the p53 tumor suppressor and is reported to regulate VEGF expression and angiogenesis. Both proteins have been considered as biomarkers and therapeutic targets for advanced solid tumors. Our work and a recent microarray-based gene profiling study suggest there could be signaling interplay between MDM2 and PSMA. We herein review the mechanisms underlining the outgrowth of tumors associated with PSMA and MDM2, their potential interaction and how this may be applied to anticancer therapeutics

Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia.

Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material.The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are typical features of neurodegenerative diseases, for example, Alzheimer's and Parkinson's diseases. An unexpected role of caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3 activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in terms of activity and subcellular localization. We demonstrate that counteracting the repressive effect of cIAP2 on caspase-3 activation, using small interfering RNA targeting cIAP2 or a SMAC mimetic such as the BV6 compound, reduced the pro-inflammatory activation of microglia cells and promoted their death. We propose that the different caspase-3 functions in microglia, and potentially other cell types, reside in the active caspase-3 complexes formed. These results also could indicate cIAP2 as a possible therapeutic target to modulate microglia pro-inflammatory activation and associated neurotoxicity observed in neurodegenerative disorders

Dkk4 and Eda Regulate Distinctive Developmental Mechanisms for Subtypes of Mouse Hair

The mouse hair coat comprises protective “primary” and thermo-regulatory “secondary” hairs. Primary hair formation is ectodysplasin (Eda) dependent, but it has been puzzling that Tabby (Eda-/y) mice still make secondary hair. We report that Dickkopf 4 (Dkk4), a Wnt antagonist, affects an auxiliary pathway for Eda-independent development of secondary hair. A Dkk4 transgene in wild-type mice had no effect on primary hair, but secondary hairs were severely malformed. Dkk4 action on secondary hair was further demonstrated when the transgene was introduced into Tabby mice: the usual secondary follicle induction was completely blocked. The Dkk4-regulated secondary hair pathway, like the Eda-dependent primary hair pathway, is further mediated by selective activation of Shh. The results thus reveal two complex molecular pathways that distinctly regulate subtype-based morphogenesis of hair follicles, and provide a resolution for the longstanding puzzle of hair formation in Tabby mice lacking Eda

nIFTy Galaxy Cluster simulations VI: The dynamical imprint of substructure on gaseous cluster outskirts

Galaxy cluster outskirts mark the transition region from the mildly non-linear cosmic web to the highly non-linear, virialised, cluster interior. It is in this transition region that the intra-cluster medium (ICM) begins to influence the properties of accreting galaxies and groups, as ram pressure impacts a galaxy's cold gas content and subsequent star formation rate. Conversely, the thermodynamical properties of the ICM in this transition region should also feel the influence of accreting substructure (i.e. galaxies and groups), whose passage can drive shocks. In this paper, we use a suite of cosmological hydrodynamical zoom simulations of a single galaxy cluster, drawn from the nIFTy comparison project, to study how the dynamics of substructure accreted from the cosmic web influences the thermodynamical properties of the ICM in the cluster's outskirts. We demonstrate how features evident in radial profiles of the ICM (e.g. gas density and temperature) can be linked to strong shocks, transient and short-lived in nature, driven by the passage of substructure. The range of astrophysical codes and galaxy formation models in our comparison are broadly consistent in their predictions (e.g. agreeing when and where shocks occur, but differing in how strong shocks will be); this is as we would expect of a process driven by large-scale gravitational dynamics and strong, inefficiently radiating, shocks. This suggests that mapping such shock structures in the ICM in a cluster's outskirts (via e.g. radio synchrotron emission) could provide a complementary measure of its recent merger and accretion history

Sources, sinks and subsidies : terrestrial carbon storage in mid-latitude fjords

This work was supported by the Natural Environment Research Council (Grant Number: NE/L501852/1) with additional support from the NERC Life Science Mass Spectrometry Facility (CEH_L_098_11_2015) and the NERC Geophysical Equipment Facility (NGGFSC Minor Loan 1031).Fjords are recognized as globally important sites for the burial and long-term storage of carbon (C) within sediments. The proximity of fjords to the terrestrial environment in combination with their geomorphology and hydrography results in the fjordic sediments being subsidized with organic carbon (OC) from the terrestrial environment. It has been well documented that terrestrial OC (OCterr) is an important component of coastal sediments, yet our understanding of the quantity of OCterr stored in these sediments remains poorly constrained. Utilizing Bayesian isotopic sediment fingerprinting techniques to the surface sediments of Loch Sunart, we estimate that 42.0 ± 10.1% of the OC is terrestrial in origin. Through combining these outputs with sedimentary OC stock estimates, we have calculated that the surface sediments (0–15 cm) hold 0.1 megaton (Mt) OCterr and estimate that the postglacial sediment held within the fjord contains 3.96 Mt OCterr. When these totals are compared to the quantity of OC stored in the adjacent terrestrial environment, it is clear that the fjord's catchment stores a greater amount of OCterr in the form of vegetation and soil. Though when normalized for area the results suggest that the marine sediments are a more effective long-term store of OCterr than the adjacent terrestrial environment. This striking result highlights the importance of the terrestrial environment as a source of OC to the coastal ocean and that the OCterr subsidy to the marine sediments is a significant mechanism for the long-term storage of OC in coastal marine sediments.Publisher PDFPeer reviewe