De Novo synthesis of VP16 coordinates the exit from HSV latency in vivo

The mechanism controlling the exit from herpes simplex virus latency (HSV) is of central importance to recurrent disease and transmission of infection, yet interactions between host and viral functions that govern this process remain unclear. The cascade of HSV gene transcription is initiated by the multifunctional virion protein VP16, which is expressed late in the viral replication cycle. Currently, it is widely accepted that VP16 transactivating function is not involved in the exit from latency. Utilizing the mouse ocular model of HSV pathogenesis together with genetically engineered viral mutants and assays to quantify latency and the exit from latency at the single neuron level, we show that in vivo (i) the VP16 promoter confers distinct regulation critical for viral replication in the trigeminal ganglion (TG) during the acute phase of infection and (ii) the transactivation function of VP16 (VP16TF) is uniquely required for the exit from latency. TG neurons latently infected with the VP16TF mutant in 1814 do not express detectable viral proteins following stress, whereas viruses with mutations in the other major viral transcription regulators ICP0 and ICP4 do exit the latent state. Analysis of a VP16 promoter/reporter mutant in the background of in 1814 demonstrates that the VP16 promoter is activated in latently infected neurons following stress in the absence of other viral proteins. These findings support the novel hypothesis that de novo expression of VP16 regulates entry into the lytic program in neurons at all phases of the viral life cycle. HSV reactivation from latency conforms to a model in which stochastic derepression of the VP16 promoter and expression of VP16 initiates entry into the lytic cycl

The impact of EU enlargement on migration flows

This document is a report commissioned by the Home Office in order to assess the magnitude of potential migration flows to the UK after the enlargement of the European Union (EU). The countries which are expected to join the EU on 1 May 2004 are Cyprus, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Malta, Poland, Slovakia and Slovenia. The aim of the report is to provide extensive information that will be helpful in evaluating the migration potential from these countries to the UK. This is done by (i) describing the socio-economic situation of the accession countries nowadays and since the early 1990s and comparing it to that of the UK and Germany, (ii) critically reviewing the existing literature that attempts to predict the effects of the current EU enlargement on migration flows, (iii) analysing the so-called Southern enlargement (the accessions of Greece, Portugal and Spain) and comparing it to the current one, and (iv) presenting a quantitative analysis of the effect of the current enlargement on migration to the UK

An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones

Herpes simplex virus (HSV) type-1 establishes lifelong latency in sensory neurones and it is widely assumed that latency is the consequence of a failure to initiate virus immediate-early (IE) gene expression. However, using a Ore reporter mouse system in conjunction with Ore-expressing HSV-1 recombinants we have previously shown that activation of the IE ICPO promoter can precede latency establishment in at least 30 % of latently infected cells. During productive infection of non-neuronal cells, IE promoter activation is largely dependent on the transactivator VP16 a late structural component of the virion. Of significance, VP16 has recently been shown to exhibit altered regulation in neurones; where its de novo synthesis is necessary for IE gene expression during both lytic infection and reactivation from latency. In the current study, we utilized the Ore reporter mouse model system to characterize the full extent of viral promoter activity compatible with cell survival and latency establishment. In contrast to the high frequency activation of representative IE promoters prior to latency establishment, cell marking using a virus recombinant expressing Ore under VP16 promoter control was very inefficient. Furthermore, infection of neuronal cultures with VP16 mutants reveals a strong VP16 requirement for IE promoter activity in non-neuronal cells, but not sensory neurones. We conclude that only IE promoter activation can efficiently precede latency establishment and that this activation is likely to occur through a VP16-independent mechanism

Post-Synthetic Modification of a Porous Hydrocarbon Cage to Give a Discrete C024 Organometallic Complex**

First published: 21 July 2022A new alkyne-based hydrocarbon cage was synthesized in high overall yield using alkyne-alkyne coupling in the cage forming step. The cage is porous and displays a moderately high BET surface area (546 m2 g−1). The cage loses crystallinity on activation and thus is porous in its amorphous form, while very similar cages have been either non-porous, or retained crystallinity on activation. Reaction of the cage with Co2(CO)8 results in exhaustive metalation of its 12 alkyne groups to give the Co24(CO)72 adduct of the cage in good yield.Chriso M. Thomas, Weibin Liang, Dan Preston, Christian J. Doonan, and Nicholas G. Whit

Correlation inequalities for classical and quantum XY models

We review correlation inequalities of truncated functions for the classical and quantum XY models. A consequence is that the critical temperature of the XY model is necessarily smaller than that of the Ising model, in both the classical and quantum cases. We also discuss an explicit lower bound on the critical temperature of the quantum XY model.Comment: 13 pages. Submitted to the volume "Advances in Quantum Mechanics: contemporary trends and open problems" of the INdAM-Springer series, proceedings of the INdAM meeting "Contemporary Trends in the Mathematics of Quantum Mechanics" (4-8 July 2016) organised by G. Dell'Antonio and A. Michelangel

Regional conditions cause contrasting behaviour in U-isotope fractionation in black shales: Constraints for global ocean palaeo-redox reconstructions

The U-isotope system is a well-established palaeo-redox proxy that potentially constrains the global extent of marine anoxia during average as well as extreme redox events throughout Earth's history. A typical archive that forms underneath a reducing water column and acts as an intense U sink is organic-rich black shale. However, the degree to which black shale archives reflect the marine U-isotope signature is not well understood because U-isotope fractionation between U(VI)-bearing seawater and U(IV)-bearing black shales may vary as a function of local environmental conditions. Here, we present a combination of U-isotope and elemental concentration datasets, supported by a complementary Mo-isotope record, for the Furlo sedimentary section in Marche–Umbria, Italy and interrogate the combined systematics to unravel the mechanisms controlling the U-isotope fractionation factor between black shales and ambient seawater. We examine black shales deposited before and during Oceanic Anoxic Event 2 (OAE 2), which was one of the most extreme climatic perturbations of the Mesozoic Era that took place around the Cenomanian–Turonian boundary (Late Cretaceous, c. 94 Ma). The results of this study show that the U-isotope signature in the black shales deposited before OAE 2 was controlled by different mechanisms than the U-isotope ratios recorded in black shales deposited during OAE 2, with both stratigraphic intervals likely influenced by local environmental conditions. Probable local environmental changes include increased U reduction associated with biomass at or above the sediment–water interface and varying dissolved hydrogen sulphide concentrations in the water column and sediment. The overall results of this study confirm that black shales are a highly complex archive for U-isotope studies of past oceanic redox conditions, due to the sensitivity of the U-isotope fractionation mechanism to local environmental conditions, which are difficult to constrain. We propose the application of a ∆238Ushale-seawater of 0.6 ± 0.1 ‰ to black shale records deposited under locally constant euxinic conditions at non-restricted settings

Functional Analysis of Aquaporin-1 Deficient Red Cells: THE COLTON-NULL PHENOTYPE

The aquaporin-1 (AQP1) water transport protein contains a polymorphism corresponding to the Colton red blood cell antigens. To define the fraction of membrane water permeability mediated by AQP1, red cells were obtained from human kindreds with the rare Colton-null phenotype. Homozygosity or heterozygosity for deletion of exon I in AQP1 correlated with total or partial deficiency of AQP1 protein. Homozygote red cell morphology appeared normal, but clinical laboratory studies revealed slightly reduced red cell life span in vivo; deformability studies revealed a slight reduction in membrane surface area. Diffusional water permeability (Pd) was measured under isotonic conditions by pulsed field gradient NMR. Osmotic water permeability (Pf) was measured by change in light scattering after rapid exposure of red cells to increased extracellular osmolality. AQP1 contributes approximately 64% (Pd = 1.5 x 10(-3) cm/s) of the total diffusional water permeability pathway, and lipid permeation apparently comprises approximately 23%. In contrast, AQP1 contributes > 85% (Pf = 19 x 10(-3) cm/s) of the total osmotic water permeability pathway, and lipid permeation apparently comprises only approximately 10%. The ratio of AQP1-mediated Pf to Pd predicts the length of the aqueous pore to be 36 A

Sustainability, certification, and regulation of biochar

Biochar has a relatively long half-life in soil and can fundamentally alter soil properties, processes, and ecosystem services. The prospect of global-scale biochar application to soils highlights the importance of a sophisticated and rigorous certification procedure. The objective of this work was to discuss the concept of integrating biochar properties with environmental and socioeconomic factors, in a sustainable biochar certification procedure that optimizes complementarity and compatibility between these factors over relevant time periods. Biochar effects and behavior should also be modelled at temporal scales similar to its expected functional lifetime in soils. Finally, when existing soil data are insufficient, soil sampling and analysis procedures need to be described as part of a biochar certification procedure.O “biochar” tem um tempo de meia-vida no solo relativamente longo e pode alterar substancialmente as propriedades, processos e funções do solo. A perspectiva da aplicação de “biochar” aos solos, em escala global, evidencia a importância de se lhe atribuir um processo de certificação sofisticado e rigoroso. O objetivo deste trabalho foi discutir o conceito da integração das propriedades do “biochar” com os fatores ambientais e socioeconômicos relevantes do local de aplicação selecionado, como parte de um procedimento de certificação sustentável que otimize a complementaridade e a compatibilidade entre esses fatores, em períodos de tempo relevantes. Os efeitos e o comportamento do “biochar” devem, também, ser modelados em escalas temporais similares às de seu tempo de vida funcional nos solos do local selecionado. Finalmente, onde os dados existentes sobre as características do solo forem insuficientes, procedimentos de amostragem e análise do solo devem ser descritos como parte do procedimento de certificação do “biochar”.publishe

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc