Formation and structure of the ferryl [Fe=O] in-termediate in the non-haem iron halogenase SyrB2: classical and QM/MM modelling agree

To rationalise mechanistically the intriguing regio- and chemoselectivity patterns for different substrates of the non-haem iron/2-oxoglutarate dependent halogenase SyrB2, it is crucial to elucidate the structure of the pivotal [FeIV[double bond, length as m-dash]O] intermediate. We have approached the problem by a combination of classical and QM/MM modelling. We present complete atomistic models of SyrB2 in complex with its native substrate L-threonine as well as L-α-amino butyric acid and L-norvaline (all conjugated to the pantetheine tether), constructed by molecular docking and extensive MD simulations. We evaluate five isomers of the [Fe[double bond, length as m-dash]O] intermediate in these simulations, with a view to identifying likely structures based on a simple “reaction distance” measure. Starting from models of the resting state, we then use QM/MM calculations to investigate the formation of the [Fe[double bond, length as m-dash]O] species for all three substrates, identifying the intermediates along the O2 activation/decarboxylation pathway on the S = 1, 2, and 3 potential-energy surfaces. We find that, despite differences in the detailed course of the reaction, essentially all pathways produce the same [Fe[double bond, length as m-dash]O] structure, in which the oxido is directed away from the substrate

The fluorine-NHC gauche effect: a structural and computational study

Herein, we report the synthesis and X-ray structural analysis of a collection of fluorinated metal N-heterocyclic carbenes (Ag, Au, Pd, Rh, Ir) and their precursor salts. The common structural feature of these species is a flanking fluoroethyl group which is either freely rotating or embedded within a bicyclic framework. Solid state analysis confirmed a gauche conformational preference in all cases with the fluorine adopting a syn clinal arrangement (ϕ[NCCF] ~ 60°) with respect to the triazolium nitrogen at the vicinal position of the NHC. A density functional theory analysis was employed to quantify these effects and evaluate the influence of electronic modulation of the carbenic carbon [(C=N+); neutral carbene (C:); metal-bound carbene (C=M)], on the relative gauche / anti preference, thus highlighting the potential of this conformational phenomenon as a useful molecular design strategy for controlling the topology of organometallic complexes

On the effect of hydrogen on the elastic moduli and acoustic loss behaviour of Ti-6Al-4V

The elastic moduli and acoustic loss behaviour of Ti-6Al-4V (wt.%) in the temperature range 5–298 K have been studied using Resonant Ultrasound Spectroscopy. A peak in the acoustic dissipation was observed at 160 K within the frequency range 250–1000 kHz. Analysis of the data acquired in this study, coupled with complementary data from the literature, showed that this was consistent with a Snoek-like relaxation process with an associated activation energy of 23 3 kJ mol. However, the loss peak was broader than would be expected for a Snoek-like relaxation, and the underlying process was shown to have a spread of relaxation times. It is suggested that this effect arises as a result of variations in the strain experienced by the phase due to different local microstructural constraint by the bounding secondary phase

Ictal asystole secondary to suspected herpes simplex encephalitis: a case report

Herpes simplex virus is a leading cause of sporadic encephalitis. While seizures are a common feature of Herpes simplex virus encephalitis, and periods of asystole have been reported in Herpes simplex virus patients, there have been no prior reports of ictal asystole secondary to such an infection

How children eat may contribute to rising levels of obesity children's eating behaviours: An intergenerational study of family influences

The term ‘obesogenic environment’ is rapidly becoming part of common phraseology. However, the influence of the family and the home environment on children's eating behaviours is little understood. Research that explores the impact of this micro environment and intergenerational influences affecting children's eating behaviours is long overdue. A qualitative, grounded theory approach, incorporating focus groups and semi-structured interviews, was used to investigate the family environment and specifically, the food culture of different generations within families. What emerged was a substantive theory based on ‘ordering of eating’ that explains differences in eating behaviours within and between families. Whereas at one time family eating was highly ordered and structured, typified by the grandparent generation, nowadays family eating behaviours are more haphazard and less ordered, evidenced by the way the current generation of children eat. Most importantly, in families with an obese child eating is less ordered compared with those families with a normal weight child. Ordering of eating' is a unique concept to emerge. It shows that an understanding of the eating process is crucial to the development and improvement of interventions targeted at addressing childhood obesity within the family context

Conversion between Triplet Pair States Is Controlled by Molecular Coupling in Pentadithiophene Thin Films

In singlet fission (SF) the initially formed correlated triplet pair state, 1(TT), may evolve toward independent triplet excitons or higher spin states of the (TT) species. The latter result is often considered undesirable from a light harvesting perspective but may be attractive for quantum information sciences (QIS) applications, as the final exciton pair can be spin-entangled and magnetically active with relatively long room temperature decoherence times. In this study we use ultrafast transient absorption (TA) and time-resolved electron paramagnetic resonance (TR-EPR) spectroscopy to monitor SF and triplet pair evolution in a series of alkyl silyl-functionalized pentadithiophene (PDT) thin films designed with systematically varying pairwise and long-range molecular interactions between PDT chromophores. The lifetime of the (TT) species varies from 40 ns to 1.5 μs, the latter of which is associated with extremely weak intermolecular coupling, sharp optical spectroscopic features, and complex TR-EPR spectra that are composed of a mixture of triplet and quintet-like features. On the other hand, more tightly coupled films produce broader transient optical spectra but simpler TR-EPR spectra consistent with significant population in 5(TT)0. These distinctions are rationalized through the role of exciton diffusion and predictions of TT state mixing with low exchange coupling J versus pure spin substate population with larger J. The connection between population evolution using electronic and spin spectroscopies enables assignments that provide a more detailed picture of triplet pair evolution than previously presented and provides critical guidance for designing molecular QIS systems based on light-induced spin coherence

Genome-Scale Oscillations in DNA Methylation during Exit from Pluripotency

Pluripotency is accompanied by the erasure of parental epigenetic memory, with naive pluripotent cells exhibiting global DNA hypomethylation both in vitro and in vivo. Exit from pluripotency and priming for differentiation into somatic lineages is associated with genome-wide de novo DNA methylation. We show that during this phase, co-expression of enzymes required for DNA methylation turnover, DNMT3s and TETs, promotes cell-to-cell variability in this epigenetic mark. Using a combination of single- cell sequencing and quantitative biophysical modeling, we show that this variability is associated with coherent, genome-scale oscillations in DNA methylation with an amplitude dependent on CpG density. Analysis of parallel single-cell transcriptional and epigenetic profiling provides evidence for oscillatory dynamics both in vitro and in vivo. These observations provide insights into the emergence of epigenetic heterogeneity during early embryo development, indicating that dynamic changes in DNA methylation might influence early cell fate decisions

PRKCA Polymorphism Changes the Neural Basis of Episodic Remembering in Healthy Individuals

Everyday functioning relies on episodic memory, the conscious retrieval of past experiences, but this crucial cognitive ability declines severely with aging and disease. Vulnerability to memory decline varies across individuals however, producing differences in the time course and severity of memory problems that complicate attempts at diagnosis and treatment. Here we identify a key source of variability, by examining gene dependent changes in the neural basis of episodic remembering in healthy adults, targeting seven polymorphisms previously linked to memory. Scalp recorded Event-Related Potentials (ERPs) were measured while participants remembered words, using an item recognition task that requires discrimination between studied and unstudied stimuli. Significant differences were found as a consequence of a Single Nucleotide Polymorphism (SNP) in just one of the tested genes, PRKCA (rs8074995). Participants with the common G/G variant exhibited left parietal old/new effects, which are typically seen in word recognition studies, reflecting recollection-based remembering. During the same stage of memory retrieval participants carrying a rarer A variant exhibited an atypical pattern of brain activity, a topographically dissociable frontally-distributed old/new effect, even though behavioural performance did not differ between groups. Results replicated in a second independent sample of participants. These findings demonstrate that the PRKCA genotype is important in determining how episodic memories are retrieved, opening a new route towards understanding individual differences in memory

Reflections on the 35th BCS Human-Computer Interaction Conference at Keele University

The following are short reflections from interactions gallery chairs, workshops organisers and members of the host organising committee