Structure of UBE2K–Ub/E3/polyUb reveals mechanisms of K48-linked Ub chain extension

Ubiquitin (Ub) chain types govern distinct biological processes. K48-linked polyUb chains target substrates for proteasomal degradation, but the mechanism of Ub chain synthesis remains elusive due to the transient nature of Ub handover. Here, we present the structure of a chemically trapped complex of the E2 UBE2K covalently linked to donor Ub and acceptor K48-linked di-Ub, primed for K48-linked Ub chain synthesis by a RING E3. The structure reveals the basis for acceptor Ub recognition by UBE2K active site residues and the C-terminal Ub-associated (UBA) domain, to impart K48-linked Ub specificity and catalysis. Furthermore, the structure unveils multiple Ub-binding surfaces on the UBA domain that allow distinct binding modes for K48- and K63-linked Ub chains. This multivalent Ub-binding feature serves to recruit UBE2K to ubiquitinated substrates to overcome weak acceptor Ub affinity and thereby promote chain elongation. These findings elucidate the mechanism of processive K48-linked polyUb chain formation by UBE2K.

Mechanochemiluminescent hydrogels for real-time visualization of chemical bond scission

Quantitative and real-time characterization of mechanically induced bond scission events taken place in polymeric hydrogels is essential to uncover their fracture mechanics. Herein, a class of mechanochemiluminescent swelling hydrogels have been synthesized through a facile micellar copolymerization method using chemiluminescent bis(adamantyl)-1,2-dioxetane (Ad) as a crosslinker. This design and synthetic strategy ensure intense mechanochemiluminescence from Ad located in a hydrophobic network inside micelles. Moreover, the mechanochemiluminescent colors can be tailored from blue to red by mixing variant acceptors. Taking advantages of the transient nature of dioxetane chemiluminescence, the damage distribution and crack evolution of the hydrogels can be visualized and analyzed with high spatial and temporal resolution. The results demonstrate the strengths of the Ad mechanophore and micellar copolymerization method in the study of damage evolution and fracture mechanism of swelling hydrogels.

Worrisome Exaggeration of Activity of Electrocatalysts Destined for Steady-State Water Electrolysis by Polarization Curves from Transient Techniques

Cyclic and linear sweep voltammetry techniques substantially misjudge the performance of water splitting electrocatalysts due to their transient nature that forbids the interface from reaching a steady-state. This misjudgment leads to the potentially detrimental yet unwittingly falsified data accumulation in the literature that requires immediate attention. Alternatively, sampled-current voltammetry (SCV) constructed from steady-state responses is advised to be widely adopted for screening electrocatalysts that are actually destined for steady-state operations. To show that this exaggeration is universal, a well-characterized activated SS, coprecipitated Co(OH)2, and Pt foil electrodes are studied for OER and HER in 1.0 M KOH. The results urge that it is time to adopt a relatively more precise alternative technique such as SCV.

Crosslinking assay to study a specific cargo-coat interaction through a transmembrane receptor in the secretory pathway v1

Intracellular trafficking through the secretory organelles depends on transient interactions between cargo proteins and transport machinery. Cytosolic coat protein complexes capture specific luminal cargo proteins for incorporation into transport vesicles by interacting with them indirectly through a transmembrane adaptor or cargo receptor. Due to their transient nature, it is difficult to study these specific ternary protein interactions just using conventional native co-immunoprecipitation. To overcome this technical challenge, we have applied a crosslinking assay to stabilize the transient and/or weak protein interactions. Here, we describe a protocol of protein cross-linking and co-immunoprecipitation, which was employed to prove the indirect interaction in the endoplasmic reticulum of a luminal secretory protein with a selective subunit of the cytosolic COPII coat through a specific transmembrane cargo receptor. This method can be extended to address other transient ternary interactions between cytosolic proteins and luminal or extracellular proteins through a transmembrane receptor within the endomembrane system.

Personal Credit and Financial Vulnerability

Rather than a narrow focus on risk of default, this paper advocates for lenders to take a broader data-led approach to tackling the challenges posed by financial vulnerability due to its latent and transient nature. Earlier identification and intervention when customers are experiencing financial hardship may help prevent default. Firstly, we consider how macro and micro data sources, in combination with emerging theoretical frameworks that conceptualise financial vulnerability, could be used by lenders for earlier identification of vulnerable customers. Secondly, we look at tailored interventions that could help financially vulnerable consumers once they have been identified, with passive and active methods inspired by protective efforts currently underway within the gambling industry. Lastly, when consumers do enter the arrears process, we highlight how lenders have a responsibility to help mitigate cognitive biases and promote behaviours that will help consumers escape perpetual debt.

Still Point of the Turning World

Schubert’s late instrumental music evokes a distinctive time-sense which not only expands the expressive potential of stylistic norms, but also invites deeper reflections on the relationship between the self and the world through his multilayered construction of temporal consciousness. The sense of now, towards which past and future gravitate, is particularly salient. In this article, I examine the formal, harmonic, topical processes through which Schubert constructs a vivid sense of the now in two movements from his late period, D. 956/ii and D. 959/ii, through the lens of phenomenology, drawing on conceptions of time as formulated by Husserl and Merleau-Ponty. I aim to bridge two fields together: first, the general theory of musical time, as has been delineated by Kramer, Barry and Clifton, which examines concepts such as linearity/nonlinearity, silence and stasis; and second, the scholarship on late Schubert, with key conceptual tools such as landscape, late style, lyricism, songfulness and interiority, formulated in the works of Adorno, Burnham, Mak and Taylor. I will also provide the cultural context of musical time in the early-nineteenth century, focusing on the wider paradigm shift from form-as-architecture to form-as-process in music. My analysis reflects a phenomenological orientation within a hermeneutic, narrative mode. I highlight the often disorienting subjective experience of time as evoked by moments that deflect from norms and expectations, specifically the tension between the transient nature of music and the sense of permanence evoked through Schubert’s cyclic, paratactic procedures. I then show how Schubert’s construal of temporal consciousness acquires a historiographical import and resonates with the broader intellectual world by framing it in terms of Schlegel’s three stages of history. I conclude by promoting phenomenological approaches in analysing Schubert’s works and nineteenth-century music at large.

The Debate of a Paṇḍita Dog with a Monk: Critique of Buddhist Monastics in üg Genre Works of Agvaanhaidav

It is in the nineteenth century that the üg genre of Mongolian literature became a favorite literary form for Mongolian writers. Most works written in this genre are didactic teachings on compassion for domestic animals, the ills of the transient nature of saṃsāra, and a critique of misconduct among Buddhist monastic communities in Mongolia. Through the words of anthropomorphized animals or even of inanimate objects, the authors of the works belonging to the üg genre expressed their social concerns and criticism of their society. One of such authors was a Mongolian monk scholar of the nineteenth century by name Agvaanhaidav (Tib: Ngag dbang mkhas grub), who in his works of the üg genre strongly advocated the development and preservation of the spirit of Mahāyāna Buddhism in Mongolia, and of the Geluk monasticism and scholarship in particular.

Inner-city possibilities: using place and space to facilitate inter-ethnic dating and romance in 1960s–1980s Leicester

Applying a spatial lens to the oral histories of heterosexual women who had intercultural romantic relationships in Leicester from the 1960s to the 1980s provides an alternative perspective on their experiences. This article examines these women's movements into and around the inner city, eliciting discussion about the concept of ‘safe’ places and spaces and the factors that determined the transient nature of these spaces. It illustrates opportunities created for intercultural mixing, away from familial gaze and public hostility. Utilizing such spaces to develop and sustain their relationships reveals a previously unacknowledged female agency that also enabled an ‘everyday multiculturalism’ in the British city.

Machine Learning Analysis of Quasi-Stationary Magnetic Fields Optically-Driven by Short Laser Pulses

Optical generation of kilo-tesla scale magnetic fields enables prospective technologies and fundamental studies with unprecedentedly high magnetic field energy density. A question is the optimal configuration of proposed setups, where plenty of physical phenomena accompany the generation and complicate both theoretical studies and experimental realizations. Short laser drivers seem more suitable in many applications, though the process is tangled by an intrinsic transient nature. In this work, an artificial neural network is engaged for unravelling main features of the magnetic field excited with a picosecond laser pulse. The trained neural network acquires an ability to read the magnetic field values from experimental data, extremely facilitating interpretation of the experimental results. The conclusion is that the short sub-picosecond laser pulse may generate a quasi-stationary magnetic field structure living on a hundred picosecond time scale, when the induced current forms a closed circuit.

Involving and engaging pregnant women in maternity-related research: reflections on an innovative approach

Background Meaningful public involvement in maternity research remains challenging, partly due to the transient nature of pregnancy. This paper reflects on the development, implementation and simple evaluation of an innovative and inclusive approach to engaging and involving pregnant and early postnatal women in research. Methods Between January and February 2018, a Research Fellow in Maternity Care, a Professor of Evidence Based Maternity Care, and a Patient and Public Involvement Lead convened for a number of meetings to discuss how public involvement and engagement might be improved for pregnancy-related research. A stakeholder group was created, including a local community matron, a community engagement officer at a local children’s centre, public contributors, and senior members of the Maternal and Child Health theme of the West Midlands Collaboration for Leadership in Applied Health Research and Care (CLAHRC WM). The team worked together to develop a format for Yoga for Bump sessions: a free 90-min session, offered weekly, which included research involvement/engagement, pregnancy yoga, and a ‘question and answer’ session with a midwife. Results A total of 67 women from two local communities in Birmingham attended Yoga for Bump sessions, which ran between May and December of 2018. Evaluation of the sessions suggested benefits to both women and researchers: it created mutually beneficial relationships between contributors and researchers, provided opportunities for women to engage and get involved in research that was directly relevant to them, and provided a convenient and efficient way for researchers to involve and engage pregnant women from diverse backgrounds in their research. Unintended benefits included self-reported improvements in women’s health and wellbeing. Conclusions Yoga for Bump demonstrates an innovative approach to engaging and involving pregnant and early postnatal women; combining a free exercise class with healthcare advice and opportunities to engage with and be involved in research, and demonstrating mutual benefits for those involved. This model has the potential to be replicated elsewhere to support inclusive public involvement in pregnancy-related research. Further work is needed to design and evaluate similar approaches to involvement/engagement and explore potential funding avenues to enhance sustainability.