The role of adenylate cyclase-associated protein in higher plant development

The Actin Cytoskeleton is essential for Eukaryotic life and is involved in a diverse range of cellular functions. Cyclase Associated Protein (CAP) was first identified in yeast as a regulator of the CYR1 Adenylate Cyclase. Subsequently CAP family members have been identified in every Eukaryotic kingdom and have also been implicated in the regulation of Actin dynamics. It has been proposed that the CAP family promotes the recycling of Actin monomers by cooperating with members of the Profilin and Actin Depolymerising Factor families. This study represents an attempt to investigate the function and developmental role of AtCAP1, an Arabidopsis member of the CAP family. Arabidopsis thaliana is widely used as a model for higher plant development due to its small sequenced genome and the availability of a wide variety of mutants. The elimination of AtCAP1 expression results in a distinct developmental phenotype. Early characteristics include the absence of the root hair collar, reduced root hair initiation and extension. Later onset phenotypes include reduced plant height and a severe reduction in pollen viability. In vivo studies of the CAP-deficient cytoskeleton reveal a distinct loss of fine filamentous Actin and the appearance of dense Actin aggregates. Cell expansion is also significantly reduced. The interaction between AtCAP1 and F-Actin is demonstrated in vitro by a biochemical interaction study and a filament bundling activity is suggested. The multimerisation of AtCAP1 and its interaction with other components of the Actin Cytoskeleton are demonstrated via Yeast Two Hybrid interactions. It is concluded that AtCAP1 is essential for the organisation of the plant cells F-Actin network and that this in turn is required for correct growth and development. It is hypothesised that AtCAP1 function is mediated by regulating the interaction between F-Actin and other Actin-interacting proteins

Ethics for A-Level

"What does pleasure have to do with morality? What role, if any, should intuition have in the formation of moral theory? If something is â simulatedâ , can it be immoral? This accessible and wide-ranging textbook explores these questions and many more. Key ideas in the fields of normative ethics, metaethics and applied ethics are explained rigorously and systematically, with a vivid writing style that enlivens the topics with energy and wit. Individual theories are discussed in detail in the first part of the book, before these positions are applied to a wide range of contemporary situations including business ethics, sexual ethics, and the acceptability of eating animals. A wealth of real-life examples, set out with depth and care, illuminate the complexities of different ethical approaches while conveying their modern-day relevance. This concise and highly engaging resource is tailored to the Ethics components of AQA Philosophy and OCR Religious Studies, with a clear and practical layout that includes end-of-chapter summaries, key terms, and common mistakes to avoid. It should also be of practical use for those teaching Philosophy as part of the International Baccalaureate. Ethics for A-Level is of particular value to students and teachers, but Fisher and Dimmockâ s precise and scholarly approach will appeal to anyone seeking a rigorous and lively introduction to the challenging subject of ethics.

Realisation of a hot carrier photovoltaic cell

The hot carrier solar cell is a heat engine; supplementing or supplanting the photovoltaic action of a traditional solar cell with a thermally driven current, analogous to a thermoelectric device. With this additional channel for energy extraction it is, in principle, possible for these cells to achieve efficiencies up to 85%, since the thermalization loss of high energy carriers is mitigated through their contribution to the heat current. In this thesis, three different hot carrier solar cell concepts are presented and experimentally investigated to probe their efficacy. Firstly, a hot carrier solar cell structure is presented, in which photogenerated carriers are extracted from a narrow band gap semiconductor to a wider bandgap semiconductor through a double barrier quantum well, providing energy selective extraction through resonant tunnelling. Current-voltage characteristics of this cell are presented along with time-resolved and temperature-dependent photoluminescence data, supporting the conclusion that this cell is operating as a hot carrier cell. Secondly, the idea of a metallic absorber for a solar cell is proposed, in order to provide ultra-high absorption of light (>99%) in metallic films thinner than 10nm. This idea is realised in two different cells, with silver and chromium absorbers. The absorption of light in the metal film, followed by extraction of heated electrons over a Schottky barrier, is demonstrated. Thirdly, the combination of these ideas is discussed, and a solar cell with a metallic absorber and selective extraction of heated electrons through resonant tunneling is realised. The current-voltage characteristics of all cells are modelled theoretically, and key signatures are revealed in both experimental and theoretical work showing the extraction of heated carriers.Open Acces

Cloned defective interfering influenza RNA and a 7 possible pan-specific treatment of respiratory virus 8 diseases

Defective interfering (DI) genomes are characterised by their ability to interfere with the 3 replication of the virus from which they were derived and other genetically compatible 4 viruses. DI genomes are synthesized by nearly all known viruses and represent a vast 5 natural reservoir of antivirals that can potentially be exploited for use in the clinic. This review 6 describes the application of DI virus to protect from virus-associated diseases in vivo using 7 as an example a highly active cloned influenza A DI genome and virus that protects broadly 8 in preclinical trials against different subtypes of influenza A and against non-influenza A 9 respiratory viruses. This influenza A-derived DI genome protects by two totally different 10 mechanisms: molecular interference with influenza A replication and by stimulating innate 11 immunity that acts against non-influenza A viruses. The review considers what is needed to 12 develop DI genomes to the point of entry into clinical trials

A statistical study of magnetic field fluctuations in the dayside magnetosheath and their dependence on upstream solar wind conditions

The magnetosheath functions as a natural interface connecting the interplanetary and magnetospheric plasma. Since the magnetosheath houses the shocked solar wind, it is populated with abundant magnetic field turbulence which are generated both locally and externally. Although the steady state magnetosheath is to date relatively well understood, the same cannot be said of transient magnetic perturbations due to their kinetic nature and often complex and numerous generation mechanisms. The current manuscript presents a statistical study of magnetic field fluctuations in the dayside magnetosheath as a function of upstream solar wind conditions. We concentrate on the ambient higher-frequency fluctuations in the range of 0.1 Hz -> 2 Hz. We show evidence that the dawn (quasi-parallel) flank is visibly prone to higher-amplitude magnetic perturbations compared to the dusk (quasi-perpendicular) region. Our statistical data also suggest that the magnitude of turbulence can be visibly enhanced close to the magnetopause during periods of southward interplanetary magnetic field orientations. Faster (> 400 km s−1) solar wind velocities also appear to drive higher-amplitude perturbations compared to slower speeds. The spatial distribution also suggests some dependence on the magnetic pileup region at the subsolar magnetopause.Peer reviewe

Live Attenuated Influenza Vaccine contains Substantial and Unexpected Amounts of Defective Viral Genomic RNA

The live attenuated influenza vaccine FluMist® was withdrawn in the USA by the Centers for Disease Control and Prevention after its failure to provide adequate protective immunity during 2013–2016. The vaccine uses attenuated core type A and type B viruses, reconfigured each year to express the two major surface antigens of the currently circulating viruses. Here Fluenz™ Tetra, the European version of this vaccine, was examined directly for defective-interfering (DI) viral RNAs. DI RNAs are deleted versions of the infectious virus genome, and have powerful biological properties including attenuation of infection, reduction of infectious virus yield, and stimulation of some immune responses. Reverse transcription polymerase chain reaction followed by cloning and sequencing showed that Fluenz™ vaccine contains unexpected and substantial amounts of DI RNA arising from both its influenza A and influenza B components, with 87 different DI RNA sequences identified. Flu A DI RNAs from segment 3 replaced the majority of the genomic full-length segment 3, thus compromising its infectivity. DI RNAs arise during vaccine production and non-infectious DI virus replaces infectious virus pro rata so that fewer doses of the vaccine can be made. Instead the vaccine carries a large amount of non-infectious but biologically active DI virus. The presence of DI RNAs could significantly reduce the multiplication in the respiratory tract of the vaccine leading to reduced immunizing efficacy and could also stimulate the host antiviral responses, further depressing vaccine multiplication. The role of DI viruses in the performance of this and other vaccines requires further investigation

A Possible Link between Turbulence and Plasma Heating

Erratum: A Possible Link between Turbulence and Plasma Heating (Astrophysical Journal (2021) 921 (65) DOI: 10.3847/1538-4357/ac1942). Astrophysical Journal, Volume 923, Issue 2, 20 December 2021, Article number 282.Numerical simulations and experimental results have shown that the formation of current sheets in space plasmas can be associated with enhanced vorticity. Also, in simulations the generation of such structures is associated with strong plasma heating. Here, we compare four-point measurements in the terrestrial magnetosheath turbulence from the Magnetospheric Multiscale mission of the flow vorticity and the magnetic field curlometer versus their corresponding one-point proxies PVI(V) and PVI(B) based on the Partial Variance of Increments (PVI) method. We show that the one-point proxies are sufficiently precise in identifying not only the generic features of the current sheets and vortices statistically, but also their appearance in groups associated with plasma heating. The method has been further applied to the region of the turbulent sheath of an interplanetary coronal mass ejection (ICME) observed at L1 by the WIND spacecraft. We observe current sheets and vorticity associated heating in larger groups (blobs), which so far have not been considered in the literature on turbulent data analysis. The blobs represent extended spatial regions of activity with enhanced regional correlations between the occurrence of conditioned currents and vorticity, which at the same time are also correlated with enhanced temperatures. This heating mechanism is substantially different from the plasma heating in the vicinity of the ICME shock, where plasma beta is strongly fluctuating and there is no vorticity. The proposed method describes a new pathway for linking the plasma heating and plasma turbulence, and it is relevant to in situ observations when only single spacecraft measurements are available.Peer reviewe

Understanding the SARS-CoV-2 virus neutralizing antibody response : lessons to be learned from HIV and respiratory syncytial virus

The SARS-CoV-2 pandemic commenced in 2019 and is still ongoing. Neither infection nor vaccination give long-lasting immunity and, here, in an attempt to understand why this might be, we have compared the neutralizing antibody responses to SARS-CoV-2 with those specific for human immunodeficiency virus type 1 (HIV-1) and respiratory syncytial virus (RSV). Currently, most of the antibodies specific for the SARS-CoV-2 S protein map to three broad antigenic sites, all at the distal end of the S trimer (receptor-binding site (RBD), sub-RBD and N-terminal domain), whereas the structurally similar HIV-1 and the RSV F envelope proteins have six antigenic sites. Thus, there may be several antigenic sites on the S trimer that have not yet been identified. The epitope mapping, quantitation and longevity of the SARS-CoV-2 S-protein-specific antibodies produced in response to infection and those elicited by vaccination are now being reported for specific groups of individuals, but much remains to be determined about these aspects of the host–virus interaction. Finally, there is a concern that the SARS-CoV-2 field may be reprising the HIV-1 experience, which, for many years, used a virus for neutralization studies that did not reflect the neutralizability of wild-type HIV-1. For example, the widely used VSV-SARS-CoV-2-S protein pseudotype has 10-fold more S trimers per virion and a different configuration of the trimers compared with the SARS-CoV-2 wild-type virus. Clarity in these areas would help in advancing understanding and aid countermeasures of the SARS-CoV-2 pandemic

Statistical study of the alteration of the magnetic structure of magnetic clouds in the Earth’s magnetosheath

The magnetosheath plays a central role in the solar wind-magnetospheric coupling. Yet the effects of its crossing on solar wind structures such as magnetic clouds (MCs) are generally overlooked when assessing their geoeffectivity. Using 82 MCs observed simultaneously in the solar wind and the magnetosheath, we carry out the first statistical study of the alteration of their magnetic structure in the magnetosheath. For each event, the bow shock properties are obtained from a magnetosheath model. The comparison between the model results and observations shows that in 80% of cases, the MHD-based model captures well the magnetosheath transition; the other events are discussed separately. We find that just downstream of the bow shock the variation of the magnetic field direction shows a very good anticorrelation (r = −0.91) with the angle between the upstream magnetic field and the shock normal. We then focus on the magnetic field north-south component Bz because of its importance for geoeffectivity. Although the sign of Bz is generally preserved in the magnetosheath, we also find evidence of long-lasting intervals of opposite Bz signs in the solar wind and the magnetosheath during some events, with a |Bz| reversal > 10 nT at the magnetopause. We find that these reversals are due to the draping of the field lines and are associated with predominant upstream By. In those cases, the estimated position of the regions of antiparallel fields along the magnetopause is independent of the sign of the upstream Bz . This may have strong implications in terms of reconnection.Peer reviewe

Cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza A virus and allows protective immunity to be established

Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI) influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus) and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 µg 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1). Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes