Upsher-Smith Laboratories (United Kingdom)

First generation students (FGS; those whose parents did not achieve a university degree) now constitute almost half of the UK university student population, but access is not synonymous with success. There is a lack of UK-specific research on factors which might explain compromised academic success in FGS compared to their continuing generation student (CGS; one or both parents achieved a university degree) peers. This study aimed to compare factors which are associated with academic success (both persistence and performance) in FGS and CGS. A sample of 133 UK university students (FGS N=79; CGS N=51) completed a survey containing measures of hope, self-efficacy, engagement and burnout. Results showed that levels of hope, engagement and burnout were similar in FGS and CGS, but that levels of self-efficacy were statistically significantly lower in FGS than CGS. Universities must urgently consider the systemic, structural and environmental barriers which cause FGS to arrive but not thrive academically. This study makes a significant contribution to knowledge about FGS in UK universities and lays the foundations for future research which aims to ensure that widening participation encompasses FGS getting on, not just getting in.

Drug compulsion manifests in some but not all individuals and implicates multifaceted processes including failures in top-down cognitive control as drivers for the hazardous pursuit of drug use in some individuals. As a closely related construct, impulsivity encompasses rash or risky behaviour without foresight and underlies most forms of drug taking behaviour, including drug use during adverse emotional states (i.e., negative urgency). While impulsive behavioural dimensions emerge from drug-induced brain plasticity, burgeoning evidence suggests that impulsivity also predates the emergence of compulsive drug use. Although the neural substrates underlying the apparently causal relationship between trait impulsivity and drug compulsion are poorly understood, significant advances have come from the interrogation of defined limbic cortico-striatal circuits involved in motivated behaviour and response inhibition, together with chemical neuromodulatory influences from the ascending neurotransmitter systems. We review what is presently known about the neurochemical mediation of impulsivity, in its various forms, and ask whether commonalities exist in the neurochemistry of compulsive drug-motivated behaviours that might explain individual risk for addiction.

Therapies based on injecting living cells into patients offer a huge potential to cure many degenerative and deadly diseases, with hundreds of clinical trials ongoing. Due to their complex nature, a basic understanding of their biochemical and functional characteristics, how to manufacture them for safe and efficacious therapy, and how to effectively implement them in clinical settings are very challenging. Raman spectroscopy could provide an information-rich, non-invasive, non-destructive analytical method to complement the use of conventional sample-based, infrequent and destructive biochemical assays typically employed to analyze and validate the quality of therapeutic cells. This article provides an overview of the current state of emerging cell therapies, and then reviews the related Raman spectroscopic state of the art analysis of human cells. This includes spectroscopic data processing considerations, the scope offered by technical variants of Raman spectroscopy, and analytical difficulties encountered by spectroscopists working with therapeutic cells. Finally, we outline a number of salient challenges as cell therapy products are translated from the laboratory to the clinic, and propose how Raman spectroscopy-based solutions could address these challenges.

Abstract Plant mitochondrial genomes vary widely in size. Although many plant mitochondrial genomes have been sequenced and assembled, the vast majority are of angiosperms, and few are of gymnosperms. Most plant mitochondrial genomes are smaller than a megabase, with a few notable exceptions. We have sequenced and assembled the 5.5 Mbp mitochondrial genome of Sitka spruce (Picea sitchensis), the largest complete mitochondrial genome of a gymnosperm. We sequenced the whole genome using Oxford Nanopore MinION, and then identified contigs of mitochondrial origin assembled from these long reads. The assembly graph shows a multipartite genome structure, composed of one smaller 168 kbp circular segment of DNA, and a larger 5.4 Mbp component with a branching structure. The assembly graph gives insight into a putative complex physical genome structure, and its branching points may represent active sites of recombination.

This article will examine the circumstances surrounding the professionalization of black hairdressing in Britain, which was relatively unknown before the 1950s. Prior to this Britain’s African and Caribbean diaspora was scattered throughout the country in small communities, warranting little attention from white hairdressers who seldom had occasion or the expertise to cut or dress black hair. All this was to change after the Second World War, with increased immigration, and the arrival of one person in particular, whose gifted musical talents endeared her to the nation. This article focuses on the role of Winifred Atwell (1914–1983) who, as a chart-topping entertainer in the British public spotlight, recognized that her appearance required high maintenance in dress, make-up and hair. As a canny entrepreneur, Atwell identified a dearth in professional black hairdressing and to facilitate her personal hair-grooming regime, opened her own salon in South London where she had other business connections. It was also an area which experienced a high volume of Caribbean settlement. Atwell’s needs and the acceleration of post-war migration were catalysts in the move from amateur domestic hairdressing to public black salons. The discussion also considers the challenges that black women faced in terms of their hair and beauty and how they sought to overcome this through visual integration with Westernized beauty ideals. It will attempt to demonstrate that Atwell became a role model through her entrepreneurship, inspiring the social aspirations of ordinary black women to establish their own businesses, professionalize their skills through training and education, and seek affiliation with white hairdressing organizations as part of a more incorporated credentialism, despite evergrowing racial tensions.

Xyloglucan (XyG) is a complex polysaccharide that is ubiquitous and often abundant in the cell walls of terrestrial plants. XyG metabolism is therefore a key component of the global carbon cycle, and hence XyG enzymology is of significant fundamental and applied importance in biomass conversion. To facilitate structure-function analyses of XyG-specific endo-glucanases, we have synthesized a 2',4'-dinitrophenyl 2-deoxy-2-fluoro-β-glycoside mechanism-based inhibitor based on the highly branched XyG repeating motif XXXG (Xyl3Glc4: ([α-d-Xylp-(1→6)]-β-d-Glcp-(1→4)-[α-d-Xylp-(1→6)]-β-d-Glcp-(1→4)-[α-d-Xylp-(1→6)]-β-d-Glcp-(1→4)-d-Glcp. Key steps in the chemo-enzymatic synthesis included selective enzyme hydrolysis of XyG polysaccharide to produce the core heptasaccharide, per-O-acetylation, α-bromination, reductive glycal formation, electrophilic fluorination, SNAr glycosylation, and Zemplen deprotection. The resulting compound, XXXG(2F)-β-DNP, specifically labelled the active sites of several endo-(xylo)glucanases by accumulation of a covalent glycosyl-enzyme intermediate, as revealed by intact protein mass spectrometry. Crystallography of a complex with a Cellvibrio japonicus Glycoside Hydrolase Family 5 (GH5) endo-xyloglucanase corroborated the covalent nature of the intermediate, and further revealed the anticipated specificity for the catalytic nucleophile of this anomeric-configuration-retaining glycosidase. This specificity complements that of an analogous XXXG N-bromoacetylglycosylamine inhibitor, which labelled the catalytic acid-base sidechain in the same enzyme [Attia, et al., Biotechnol. Biofuels, 2018, 11, 45]. We anticipate that these inhibitors may find continued use in mechanistic analyses of endo-(xylo)glucanases from diverse GH families.

Protein interactions shape proteome function and thus biology. Identification of protein interactions is a major goal in molecular biology, but biochemical methods, although improving, remain limited in coverage and accuracy. Whereas computational predictions can guide biochemical experiments, low validation rates of predictions remain a major limitation. Here, we investigated computational methods in the prediction of a specific type of interaction, the inhibitory interactions between proteases and their inhibitors. Proteases generate thousands of proteoforms that dynamically shape the functional state of proteomes. Despite the important regulatory role of proteases, knowledge of their inhibitors remains largely incomplete with the vast majority of proteases lacking an annotated inhibitor. To link inhibitors to their target proteases on a large scale, we applied computational methods to predict inhibitory interactions between proteases and their inhibitors based on complementary data, including coexpression, phylogenetic similarity, structural information, co-annotation, and colocalization, and also surveyed general protein interaction networks for potential inhibitory interactions. In testing nine predicted interactions biochemically, we validated the inhibition of kallikrein 5 by serpin B12. Despite the use of a wide array of complementary data, we found a high false positive rate of computational predictions in biochemical follow-up. Based on a protease-specific definition of true negatives derived from the biochemical classification of proteases and inhibitors, we analyzed prediction accuracy of individual features, thereby we identified feature-specific limitations, which also affected general protein interaction prediction methods. Interestingly, proteases were often not coexpressed with most of their functional inhibitors, contrary to what is commonly assumed and extrapolated predominantly from cell culture experiments. Predictions of inhibitory interactions were indeed more challenging than predictions of nonproteolytic and noninhibitory interactions. In summary, we describe a novel and well-defined but difficult protein interaction prediction task and thereby highlight limitations of computational interaction prediction methods.

Blood banking is an essential aspect of modern medical care. When red blood cells (RBCs) are stored, they become damaged by various chemical processes, such as accumulation of their own waste products and oxidative injury, among others. These processes lead to the development of the RBC storage lesion, a complex condition where the severity is reflected through the morphology of the stored cells. It was hypothesized that Raman spectroscopy could be used to monitor certain structural and compositional changes associated with such ageing effects and that a relationship between these features and traditional morphology (as measured using a morphology index) could be observed. The hypothesis was tested by measuring spectral features associated with hemoglobin oxygenation from dry-fixed smears and liquid RBCs for twenty-nine different donors (combined), and comparing the trends with morphological scoring from seven of these donors. After appropriately fitting the two data sets to either power or linear curves, the oxygenation state was shown to change in a manner that was donor-dependent and that closely tracked morphological changes. This study suggests Raman analysis has promise for providing a rapid and objective measure of the cell quality of stored RBCs through measurements of hemoglobin oxygenation that is comparable to traditional morphological assessment.

ABSTRACTRemarkably little is known about the earliest surviving separate-sheet medieval map of Britain that takes its name from its former owner, Richard Gough (1735–1809), and that has been variously dated to between 1300 and 1400, and later. It presents a sophisticated cartographical image at a time when detailed maps of individual regions were almost unknown in Europe, yet nothing is agreed about its possible origins, context (ecclesiastical or secular), or why and how it was compiled. In the belief that historical interpretation has to stem from an intimate knowledge of the map as artefact—the state of the parchment, nature of the inks, palaeography—as well as image, an informal study group of historians and scientists (the Gough Map Panel) was convened in 2012 to examine the map through high resolution digital reproduction, hyperspectral analysis, three-dimensional analysis and Raman pigment analysis. Although the study is still ongoing, much that is new has been discovered, notably about the way features were marked on the map, Gough’s application to the map of a damaging reagent to render place-names readable, and the extent to which the original map (now dated to c.1400), although never completed, was nonetheless reworked on two different occasions in the fifteenth century, effectively creating two further maps. These and other findings are summarized here to encourage the further study of the map’s features that is needed before it can be fully understood.