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

Mind over memory: cueing the aging brain

A decline in recollection is a hallmark of even healthy aging and is associated with wider impairments in mental control. Older adults have difficulty internally directing thought and action in line with their goals, and often rely more on external cues. To assess the impact this has on memory, emerging brain-imaging and behavioral approaches investigate the operation and effectiveness of goal-directed control before information is retrieved. Current data point to effects of aging at more than one stage in this process, particularly in the face of competing goals. These effects may reflect wider changes in the proactive, self-initiated regulation of thought and action. Understanding them is essential for establishing whether internal “self-cuing” of memory can be improved, and whether—and when—it is best to use environmental support from external cues to maximize memory performance

Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells

Through the histone methyltransferase EZH2, the Polycomb complex PRC2 mediates H3K27me3 and is associated with transcriptional repression. PRC2 regulates cell-fate decisions in model organisms; however, its role in regulating cell differentiation during human embryogenesis is unknown. Here, we report the characterization of $\small \textit{EZH2}$-deficient human embryonic stem cells (hESCs). H3K27me3 was lost upon $\small \textit{EZH2}$ deletion, identifying an essential requirement for EZH2 in methylating H3K27 in hESCs, in contrast to its non-essential role in mouse ESCs. Developmental regulators were derepressed in $\small \textit{EZH2}$-deficient hESCs, and single-cell analysis revealed an unexpected acquisition of lineage-restricted transcriptional programs. $\small \textit{EZH2}$-deficient hESCs show strongly reduced self-renewal and proliferation, thereby identifying a more severe phenotype compared to mouse ESCs. $\small \textit{EZH2}$-deficient hESCs can initiate differentiation toward developmental lineages; however, they cannot fully differentiate into mature specialized tissues. Thus, $\small \textit{EZH2}$ is required for stable ESC self-renewal, regulation of transcriptional programs, and for late-stage differentiation in this model of early human development.Wellcome Trust (Grant ID: WT093736), Biotechnology and Biological Sciences Research Council (Grant ID: BBS/E/B/000C0402), Medical Research Council (DTG Studentships, Grant ID: MR/J003808/1

Fluoride and oral health

The discovery during the first half of the 20th century of the link between natural fluoride, adjusted fluoride levels in drinking water and reduced dental caries prevalence proved to be a stimulus for worldwide on-going research into the role of fluoride in improving oral health. Epidemiological studies of fluoridation programmes have confirmed their safety and their effectiveness in controlling dental caries. Major advances in our knowledge of how fluoride impacts the caries process have led to the development, assessment of effectiveness and promotion of other fluoride vehicles including salt, milk, tablets, toothpaste, gels and varnishes. In 1993, the World Health Organization convened an Expert Committee to provide authoritative information on the role of fluorides in the promotion of oral health throughout the world (WHO TRS 846, 1994). This present publication is a revision of the original 1994 document, again using the expertise of researchers from the extensive fields of knowledge required to successfully implement complex interventions such as the use of fluorides to improve dental and oral health. Financial support for research into the development of these new fluoride strategies has come from many sources including government health departments as well as international and national grant agencies. In addition, the unique role which industry has played in the development, formulation, assessment of effectiveness and promotion of the various fluoride vehicles and strategies is noteworthy. This updated version of ‘Fluoride and Oral Health’ has adopted an evidence-based approach to its commentary on the different fluoride vehicles and strategies and also to its recommendations. In this regard, full account is taken of the many recent systematic reviews published in peer reviewed literature

Electrophysiological Dissociation of Picture Versus Word Encoding: The Distinctiveness Heuristic as a Retrieval Orientation

Event-related potentials (ERPs) were used to investigate the neural processes underlying the distinctiveness heuristic— a response mode in which participants expect to remember vivid details of an experience and make recognition decisions based on this metacognitive expectation. One group of participants studied pictures and auditory words; another group studied visual and auditory words. Studied and novel items were presented at test as words only, with all novel items repeating after varying lags. ERP differences were seen between the word and picture groups for both studied and novel items. For the novel items, ERP differences were largest in frontal and central midline electrodes. In separate analyses, the picture group showed the greatest ERP differences between item types in a parietally based component from 550 to 1000 msec, whereas the word group showed the greatest differences in a frontally based component from 1000 to 2000 msec. The authors suggest that the distinctiveness heuristic is a retrieval orientation that facilitates reliance upon recollection to differentiate between item types. Although the picture group can use this heuristic and its retrieval orientation on the basis of recollection, the word group must engage additional postretrieval processes to distinguish between item types, reflecting the use of a different retrieval orientation.Psycholog

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

Social Disparities in Private Renting Amongst Young Families in England and Wales, 2001-2011

This is the final version of the article. It first appeared from Taylor & Francis via https://doi.org/10.1080/14036096.2016.1242511In Britain, the proportion of young families living in the private rented sector (PRS) has risen sharply in recent years. There is mounting concern that this trend could be particularly pronounced amongst less advantaged young families, who may be disproportionately channelled into relatively costly, insecure and lower quality accommodation in the PRS by growing difficulties accessing other tenures. In consequence, this paper uses the Office for National Statistics Longitudinal Study of England and Wales to compare how family structure and socio-economic characteristics shaped rates of private renting amongst young adults heading families in 2001 and 2011. The results show that social disparities generally increased during this period as private renting expanded most rapidly amongst some types of lone parent and amongst young adults heading couple families with a less advantaged class position. Increasing housing inequalities between young people may thus be as much a feature of “Generation Rent” as deepening divides between generations.This work was supported by an Economic and Social Research Council (ESRC) Future Research Leaders award [grant number ES/L009498/1]. Additional financial support was provided by the Isaac Newton Trust

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline.

Adult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells (NSPCs). An improved understanding of the underlying mechanisms that drive age-associated neurogenic deficiency could lead to the development of strategies to alleviate cognitive impairment and facilitate neuroregeneration. An essential step towards this aim is to investigate the molecular changes that occur in NSPC aging on a genomewide scale. In this study, we compare the transcriptional, histone methylation and DNA methylation signatures of NSPCs derived from the subventricular zone (SVZ) of young adult (3 months old) and aged (18 months old) mice. Surprisingly, the transcriptional and epigenomic profiles of SVZ-derived NSPCs are largely unchanged in aged cells. Despite the global similarities, we detect robust age-dependent changes at several hundred genes and regulatory elements, thereby identifying putative regulators of neurogenic decline. Within this list, the homeobox gene Dbx2 is upregulated in vitro and in vivo, and its promoter region has altered histone and DNA methylation levels, in aged NSPCs. Using functional in vitro assays, we show that elevated Dbx2 expression in young adult NSPCs promotes age-related phenotypes, including the reduced proliferation of NSPC cultures and the altered transcript levels of age-associated regulators of NSPC proliferation and differentiation. Depleting Dbx2 in aged NSPCs caused the reverse gene expression changes. Taken together, these results provide new insights into the molecular programmes that are affected during mouse NSPC aging, and uncover a new functional role for Dbx2 in promoting age-related neurogenic decline.This work was supported by grants to P.J.R.-G. from the 6 Wellcome Trust (WT093736) and the BBSRC (BB/P013406/1, BB/M022285/1), by funding from 7 Sapienza University of Rome (G.L, S.B., E.C) and by a grant from the Spanish Ministry of 8 Economy to P.B. (BFU2016-75412-R, co-financed by FEDER). The Babraham Institute Biological 9 Services Unit is supported by Campus Capability Grant funding from the BBSRC

Austerity urbanism and Olympic counter-legacies: gendering, defending and expanding the urban commons in East London

This article reflects on an occupation led by single mothers to contest the destruction of social housing in post-Olympics East London. In the process, it argues for a more gendered theorisation of the urban commons. Drawing on auto-ethnography, participant observation and qualitative interviews, the article argues three central points: First, that the occupation demonstrates the gendered nature of the urban commons and the leadership of women in defending them from enclosure; second that the defence of an existing urban commons enabled the creation of a new temporary commons characterised by the collectivisation of gendered socially reproductive activities; and third that this commoning has had a lasting impact on housing activism at the city scale and beyond. This impact is conceptualised as an ‘Olympic counter-legacy’ that is characterised by the forging of new relationships and affinities, the strengthening of networked activism and circulation of tactics between campaign groups