Methylation of elongation factor 1α in mouse 3T3B and 3T3BSV40 cells

AbstractTwo-dimensional gel electrophoretic (NEPHGE) analysis of proteins from mouse 3T3B and 3T3B/SV40 cells labelled with [methyl-3H]methionine in the presence of cycloheximide have revealed that the elongation factor 1α (EF-1α) in these cells is methylated and that the extent of methylation is higher in the SV40 transformed cell type. It is suggested that methylation may account for differences in growth properties for the different cell types

Conserved charges and supersymmetry in principal chiral and WZW models

Conserved and commuting charges are investigated in both bosonic and supersymmetric classical chiral models, with and without Wess-Zumino terms. In the bosonic theories, there are conserved currents based on symmetric invariant tensors of the underlying algebra, and the construction of infinitely many commuting charges, with spins equal to the exponents of the algebra modulo its Coxeter number, can be carried out irrespective of the coefficient of the Wess-Zumino term. In the supersymmetric models, a different pattern of conserved quantities emerges, based on antisymmetric invariant tensors. The current algebra is much more complicated than in the bosonic case, and it is analysed in some detail. Two families of commuting charges can be constructed, each with finitely many members whose spins are exactly the exponents of the algebra (with no repetition modulo the Coxeter number). The conserved quantities in the bosonic and supersymmetric theories are only indirectly related, except for the special case of the WZW model and its supersymmetric extension.Comment: LaTeX; 49 pages; v2: minor changes and additions to text and ref

Leveraging sponsorship to achieve consumer relationship objectives through the creation of ‘marketing spaces’: An exploratory study

This paper explores the emergence of sponsorship-linked events as a strategy to leverage relational outcomes through sponsorship investment. The growing use of sponsorship-linked events reinforces the need to understand the potential of such leverage strategies, thus the findings contribute to the body of literature on effective sponsorship practices. Findings from semi-structured interviews with Sponsorship and Marketing Managers suggest a shifting orientation among sponsors towards the pursuit of relational objectives. The privileged access to consumers afforded through sponsorship allows sponsors to manufacture opportunities to create intimacy with customers through sponsorship-linked events in relaxed, comfortable environments; thus sponsorship-linked events are positioned as a rich environment to add value to consumer–brand interactions and achieve relational objectives. Hosting specifically designed events affords sponsors an increased modicum of control over consumer–brand experiences in sponsorship environments characterised by a lack of control over sponsored property actions. However, this control may be eroded by social media technologies, which facilitate consumer–consumer communication around sponsorship-linked events. Social media, however, is proposed as a useful tool to elicit consumer feedback, addressing the misalignment between current sponsorship evaluation practices and emergent relational objectives revealed in the empirical findings. Therefore, successfully activating the sponsorship-linked marketing space demands an integrated and strategic approach

Exawatt-Zettawatt Pulse Generation and Applications

A new amplification method, weaving the three basic compression techniques, Chirped Pulse Amplification (CPA), Optical Parametric Chirped Pulse Amplification (OPCPA) and Plasma Compression by Backward Raman Amplification (BRA) in plasma, is proposed. It is called C3 for Cascaded Conversion Compression. It has the capability to compress with good efficiency kilojoule to megajoule, nanosecond laser pulses into femtosecond pulses, to produce exawatt and beyond peak power. In the future, C3 could be used at large-scale facilities such as the National Ignition Facility (NIF) or the Laser Megajoule (LMJ) and open the way to zettawatt level pulses. The beam will be focused to a wavelength spot size with a f#1. The very small beam size, i.e. few centimeters, along with the low laser repetition rate laser system will make possible the use of inexpensive, precision, disposable optics. The resulting intensity will approach the Schwinger value, thus opening up new possibilities in fundamental physics.Comment: 13 pages, 4 figure

Molecular simulation of chevrons in confined smectic liquid crystals

Chevron structures adopted by confined smectic liquid crystals are investigated via molecular dynamics simulations of the Gay-Berne model. The chevrons are formed by quenching nematic films confined between aligning planar substrates whose easy axes have opposing azimuthal components. When the substrates are perfectly smooth, the chevron formed migrates rapidly towards one of the confining walls to yield a tilted layer structure. However, when substrate roughness is included, by introducing a small-amplitude modulation to the particle- substrate interaction well-depth, a symmetric chevron is formed which remains stable over sufficiently long runtimes for detailed structural information, such as the relevant order parameters and director orien- tation, to be determined. For both smooth and rough boundaries, the smectic order parameter remains non-zero across the entire chevron, implying that layer identity is maintained across the chevron tip. Also, when the surface-stabilised chevron does eventually revert to a tilted layer structure, it does so via surface slippage, such that layer integrity is maintained throughout the chevron to tilted layer relaxation process. </p

Recruitment, retention, and training of people with type 2 diabetes as diabetes prevention mentors (DPM) to support a healthcare professional-delivered diabetes prevention program:The Norfolk Diabetes Prevention Study (NDPS)

Objective: Intensive lifestyle interventions reduce the risk of type 2 diabetes in populations at highest risk, but staffing levels are usually unable to meet the challenge of delivering effective prevention strategies to a very large at-risk population. Training volunteers with existing type 2 diabetes to support healthcare professionals deliver lifestyle interventions is an attractive option. Methods: We identified 141 973 people at highest risk of diabetes in the East of England, screened 12 778, and randomized 1764 into a suite of type 2 diabetes prevention and screen detected type 2 diabetes management trials. A key element of the program tested the value of volunteers with type 2 diabetes, trained to act as diabetes prevention mentors (DPM) when added to an intervention arm delivered by healthcare professionals trained to support participant lifestyle change. Results: We invited 9951 people with type 2 diabetes to become DPM and 427 responded (4.3%). Of these, 356 (83.3%) were interviewed by phone, and of these 131 (36.8%) were interviewed in person. We then appointed 104 of these 131 interviewed applicants (79%) to the role (mean age 62 years, 55% (n=57) male). All DPMs volunteered for a total of 2895 months, and made 6879 telephone calls to 461 randomized participants. Seventy-six (73%) DPMs volunteered for at least 6 months and 66 (73%) for at least 1 year. Discussion: Individuals with type 2 diabetes can be recruited, trained and retained as DPM in large numbers to support a group-based diabetes prevention program delivered by healthcare professionals. This volunteer model is low cost, and accesses the large type 2 diabetes population that shares a lifestyle experience with the target population. This is an attractive model for supporting diabetes prevention efforts

Panspermia, Past and Present: Astrophysical and Biophysical Conditions for the Dissemination of Life in Space

Astronomically, there are viable mechanisms for distributing organic material throughout the Milky Way. Biologically, the destructive effects of ultraviolet light and cosmic rays means that the majority of organisms arrive broken and dead on a new world. The likelihood of conventional forms of panspermia must therefore be considered low. However, the information content of dam-aged biological molecules might serve to seed new life (necropanspermia).Comment: Accepted for publication in Space Science Review

The Tarantula massive binary monitoring: III. Atmosphere analysis of double-lined spectroscopic systems

Context. Accurate stellar parameters of individual objects in binary systems are essential to constrain the effects of binarity on stellar evolution. These parameters serve as a prerequisite to probing existing and future theoretical evolutionary models. Aims. We aim to derive the atmospheric parameters of the 31 double-lined spectroscopic binaries in the Tarantula Massive Binary Monitoring sample. This sample, composed of detached, semi-detached and contact systems with at least one of the components classified as an O-type star, is an excellent test-bed to study how binarity can impact our knowledge of the evolution of massive stars. Methods. In the present paper, 32 epochs of FLAMES/GIRAFFE spectra are analysed by using spectral disentangling to construct the individual spectra of 62 components. We then apply the CMFGEN atmosphere code to determine their stellar parameters and their helium, carbon, and nitrogen surface abundances. Results. Among the 31 systems that we study in the present paper, we identify between 48 and 77% of them as detached, likely pre-interacting systems, 16% as semi-detached systems, and between 5 and 35% as systems in or close to contact phase. Based on the properties of their components, we show that the effects of tides on chemical mixing are limited. Components on longer-period orbits show higher nitrogen enrichment at their surface than those on shorter-period orbits, in contrast to expectations of rotational or tidal mixing, implying that other mechanisms play a role in this process. For semi-detached systems, components that fill their Roche lobe are mass donors. They exhibit higher nitrogen content at their surface and rotate more slowly than their companions. By accreting new material, their companions spin faster and are likely rejuvenated. Their locations in the N − v sin i diagram tend to show that binary products are good candidates to populate the two groups of stars (slowly rotating, nitrogen-enriched objects and rapidly rotating non-enriched objects) that cannot be reproduced through single-star population synthesis. Finally, we find no peculiar surface abundances for the components in (over-)contact systems, as has been suggested by evolutionary models for tidal mixing. Conclusions. This sample, consisting of 31 massive binary systems, is the largest sample of binaries composed of at least one O-type star to be studied in such a homogeneous way by applying spectral disentangling and atmosphere modelling. The study of these objects gives us strong observational constraints to test theoretical binary evolutionary tracks

Terminal regions confer plasticity to the tetrameric assembly of human HspB2 and HspB3

Heterogeneity in small heat shock proteins (sHsps) spans multiple spatiotemporal regimes – from fast fluctuations of part of the protein, to conformational variability of tertiary structure, plasticity of the interfaces, and polydispersity of the inter-converting, and co-assembling oligomers. This heterogeneity and dynamic nature of sHsps has significantly hindered their structural characterisation. Atomic-coordinates are particularly lacking for vertebrate sHsps, where most available structures are of extensively truncated homomers. sHsps play important roles in maintaining protein levels in the cell and therefore in organismal health and disease. HspB2 and HspB3 are vertebrate sHsps that are found co-assembled in neuromuscular cells, and variants thereof are associated with disease. Here, we present the structure of human HspB2/B3, which crystallised as a hetero-tetramer in a 3:1 ratio. In the HspB2/B3 tetramer, the four a-crystallin domains (ACDs) assemble into a flattened tetrahedron which is pierced by two non-intersecting approximate dyads. Assembly is mediated by flexible “nuts and bolts” involving IXI/V motifs from terminal regions filling ACD pockets. Parts of the N-terminal region bind in an unfolded conformation into the anti-parallel shared ACD dimer grooves. Tracts of the terminal regions are not resolved, most likely due to their disorder in the crystal lattice. This first structure of a full-length human sHsp heteromer reveals the heterogeneous interactions of the terminal regions and suggests a plasticity that is important for the cytoprotective functions of sHsps

DNA methylation is required to maintain both DNA replication timing precision and 3D genome organization integrity

DNA replication timing and three-dimensional (3D) genome organization are associated with distinct epigenome patterns across large domains. However, whether alterations in the epigenome, in particular cancer-related DNA hypomethylation, affects higher-order levels of genome architecture is still unclear. Here, using Repli-Seq, single-cell Repli-Seq, and Hi-C, we show that genome-wide methylation loss is associated with both concordant loss of replication timing precision and deregulation of 3D genome organization. Notably, we find distinct disruption in 3D genome compartmentalization, striking gains in cell-to-cell replication timing heterogeneity and loss of allelic replication timing in cancer hypomethylation models, potentially through the gene deregulation of DNA replication and genome organization pathways. Finally, we identify ectopic H3K4me3-H3K9me3 domains from across large hypomethylated domains, where late replication is maintained, which we purport serves to protect against catastrophic genome reorganization and aberrant gene transcription. Our results highlight a potential role for the methylome in the maintenance of 3D genome regulation