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DNA aptamer AptERA 2 targets ERA from Staphylococcus aureus and limits GTP hydrolysis
Get PDFRibosome assembly is a multistep process that ensures a functional ribosome structure. The molecular mechanism that ribosomeassociated GTPases (RAGTPases) use to enhance ribosome assembly accuracy remains largely to be elucidated. Here, we use systematic evolution of ligands by exponential enrichment (SELEX), followed by sequencing, comprehensive bioinformatics analysis, and biochemical characterization to identify aptamers that target the RA-GTPase ERA of Staphylococcus aureus. ELONA and thermophoresis assays show that the AptERA 2 interaction with ERA is in the 200 nM range of affinity, displays a high level of specificity, and depends on the target structure. Docking to ERA suggests that AptERA 2 interacts with the protein’s KH domain, consistent with the aptamer’s similarities with helix 45 of the 16S rRNA. AptERA 2 did interact with the isolated KH domain but did not bind to the ∆KH ERA nor to the similar RA-GTPase RbgA, which shares the GTPase core but lacks the KH domain, confirming that the aptamer recognizes and binds the KH domain of ERA. This interaction leads to a significant reduction of 30S-dependent GTP hydrolysis, indicative of allosteric modulation of the enzyme activity or limiting ERA binding or the KH domain interaction with the 3’ end of the 16S rRNA rather than directly blocking GTP binding. Altogether, this work highlights the versatility of aptamers as tools to understand the complex processes of ribosome biogenesis further, offering new insights into bacterial protein synthesis mechanisms
Circular dichroism and multiphoton circularly polarized luminescence switching using a bis‐perylene diimide macrocycle
Get PDFChiroptical switches exhibit stimuli-induced changes in the sign or strength of their circular dichroism (CD) or circularly polarized luminescence (CPL) and are materials with significant potential for chiroptical sensing and biological imaging. However, the chromophores used in chiroptical materials usually require excitation by ultraviolet or visible light, which results in higher cytotoxicity and lower penetration compared to near-infrared (NIR) photoexcitation. This can be overcome by multiphoton excitation, yet multiphoton CPL (MP-CPL) has been challenging to measure in organic emitters. Core-twisted perylene diimides (PDIs) are excellent chromophores with which to develop MP-CPL emitters due to a chiral π-system capable of two-photon absorption. Furthermore, the integration of these chiral PDIs into stimuli-responsive macrocycles affords configurational stability and the potential for chiroptical switching, due to the chromophore's tuneable chiral conformation. In this work we report a chiral bis-PDI macrocycle with stable, yet conformationally dynamic, enantiomers, and in doing so realize a novel chiroptical material that combines switchable CD and MP-CPL for the first time
Transforming African food systems: perspectives from the Food Systems Network for Africa (FSNet-Africa)
Get PDFAfrican food systems face significant challenges, including poverty, inequality, climate change, and unsustainable practices. To ensure access to safe and nutritious food while addressing socio-economic and environmental issues, fundamental changes are necessary. A collaborative and inclusive research agenda that engages diverse stakeholders through case-study research, aligning with continent-wide frameworks such as Agenda 2063, the CAADP, and the Sustainable Development Goals (SDGs), is vital. There are few cross-case analyses that bring together empirical case study research to evaluate and provide holistic appraisals of African food systems. This perspectives paper aims to provide such a synthesis from the empirical case studies generated under the Food Systems Research Network for Africa (FSNet-Africa) project. 19 case study projects in six African countries, were conducted by 83 researchers. Five key focus areas were identified: food system governance, indigenous crops and African foods, innovations for sustainable production among small-scale farmers, consumer preferences, and food loss and waste. The findings emphasise an urgent need for collaboration to address food security and nutrition challenges in Africa. Major priorities for transforming African food systems include inclusive engagement and the integration of indigenous knowledge to improve local food choices and resilience, and reducing food loss through capacity-building efforts and changing perceptions of waste. Future research should focus on governance, indigenous crops, and innovations in sustainable production to drive a transformative shift in African food systems. These priority areas will be critical for the next global and regional development agenda, reflecting the needs and aspirations of underrepresented communities across Africa
Cardiovascular risk factors management in older adults: a clinical consensus statement from the European Association of Preventive Cardiology of the ESC and the ESC Council for Cardiology Practice
Get PDFCardiovascular disease (CVD) currently ranks first in global mortality and morbidity and its prevalence increases with age. The most common risk factors for CVD are hypertension, diabetes mellitus, dyslipidaemias, adipositas, smoking, and physical inactivity, Also, depression, anaemia and frailty can be considered important risk factors for CVD. Incidence and prevalence of risk factors and comorbidities increase with age. Nevertheless, risk factor management in older adults and how intensively they should be treated are challenging for cardiovascular specialists and other clinicians, and an intensive and individual approach is needed, given the limited evidence available to date.
Therefore, in this clinical consensus document from the European Association of Preventive Cardiology of ESC and ESC Council for Cardiology Practice, a modern reappraisal of the evidence on the field is provided, together with simple, practical, and feasible suggestions to achieve the best goal in the clinical setting, focusing on evidence-based concepts
A method to identify positive tipping points to accelerate low-carbon transitions and actions to trigger them
Get PDFMeeting the Paris Agreement to limit global warming to “well below 2 °C” requires a radical acceleration of action, as the global economy is decarbonising at least five times too slowly. Tipping points, where low-carbon transitions become self-propelling, could be key to achieving the necessary acceleration. We deem these normatively ‘positive’, because they can limit considerable, inequitable harms from global warming and help achieve sustainability. Some positive tipping points, such as the UK’s elimination of coal power, have already been reached at national and sectoral scales. The challenge now is to credibly identify further potential positive tipping points, and the actions that can bring them forward, whilst avoiding wishful thinking about their existence, or oversimplification of their nature, drivers, and impacts. Hence, we propose a methodology for identifying potential positive tipping points, assessing their proximity, identifying the factors that can influence them, and the actions that can trigger them. Building on relevant research, this ‘identifying positive tipping points’ (IPTiP) methodology aims to establish a common framework that we invite fellow researchers to help refine, and practitioners to apply. To that end, we offer suggestions for further work to improve it and make it more applicable
The role of community pharmacists in medicines optimisation for housebound people: a scoping review
Get PDFBackground
An increasingly ageing population presents many challenges for healthcare systems
including how to support older adults who are more likely to be both housebound and
have complex medication needs. Community pharmacists may play a key role in
medicines optimisation for this vulnerable population, however, the extent of
literature exploring this topic is unclear.
Objective
To map existing literature on the role of community pharmacists in medicines
optimization for housebound older adults in the United Kingdom (UK).
Methods
A scoping review was conducted following PRISMA-ScR guidelines. Peer-reviewed
primary research and grey literature published since 2000 were searched using
relevant databases and websites. Data was charted using a standardised form
based on TIDieR guidelines and EPOC taxonomies. A narrative synthesis was
conducted to summarise and interpret the findings from included studies.
Results
Seven sources were included in the review - five peer-reviewed articles and two grey
literature reports. Interventions consisted of domiciliary medication reviews
conducted by pharmacists. Key medicines optimization strategies addressed were
medication review, deprescribing, addressing polypharmacy and facilitating
communication between providers. Reported outcomes included identification of
widespread issues with polypharmacy and medication-related problems, reduced
hospital admissions, cost savings and improved patient care. Gaps identified were limited generalizability, lack of comparisons to standard care, and under-
representation of minority groups.
Conclusions
The literature indicates promise for the role of community pharmacists in medicines
optimization for housebound older adults through domiciliary services. However,
more research is needed to evaluate the effectiveness and feasibility of pharmacist-
led interventions in this setting. Addressing identified gaps will help inform
pharmacists' roles in supporting medication needs of housebound patients
The Emotional Labour of International Criminal Lawyers
Get PDFEmotional labour — the management of feelings for the purpose of creating an institutionally acceptable public display — has received growing attention in legal scholarship. Although the role of emotion has been increasingly acknowledged in relation to lawyers well-being, emotional labour itself remains under-theorized as a constitutive element of professionalism, particularly in an international context. This article contributes to the development of this emerging field by examining emotional labour within the practice of international criminal law (ICL). Drawing upon original interviews, an analysis of professional codes of conduct, and the normative expectations embedded in legal roles, we demonstrate that emotional labour is both pervasive and institutionally unacknowledged in ICL. We explore how it is performed across different roles and sites, and how its uneven recognition affects practitioners, stakeholders and institutions. By foregrounding emotional labour as a professional competency — rather than framing it solely in terms of well-being — this study advances a broader understanding of legal professionalism, offering insights relevant to complex and challenging legal settings and other ‘extreme work’ environments
Breather interactions in the integrable discrete Manakov system and trigonometric Yang–Baxter maps
Get PDFThe goal of this work is to obtain a complete characterization of soliton and breather interactions in the integrable discrete Manakov (IDM) system, a vector generalization of the Ablowitz-Ladik model. The IDM system, which in the continuous limit reduces to the Manakov system (i.e., a 2-component vector nonlinear Schrödinger equation), was shown to admit a variety of discrete vector soliton solutions: fundamental solitons, fundamental breathers, and composite breathers. While the interaction of fundamental solitons was studied early on, no results are presently available for other types of soliton-breather and breather-breather interactions. Our study reveals that upon interacting with a fundamental breather, a fundamental soliton becomes a fundamental breather. Conversely, the interaction of two fundamental breathers generically yields two fundamental breathers with polarization shifts, but may also result in a fundamental soliton and a fundamental breather. Composite breathers interact trivially both with each other and with a fundamental soliton or breather. Explicit formulas for the scattering coefficients that characterize fundamental and composite breathers are given. This allows us to interpret the interactions in terms of a refactorization problem and derive the associated Yang–Baxter maps describing the effect of interactions on the polarizations. These give the first examples of parametric Yang–Baxter maps of trigonometric type
Carsharing Models and Influences – A Literature Review
Get PDFThis report is a literature review of car sharing models, exploring the operational, regulatory and financial differences between different models of shared access to cars and how this compares to individual ownership. The report was commissioned by INFUZE [UKRI-EPSRC grant number: EP/Z531273/1] and completed by Connected Places Catapult
Aeolian–fluvial interactions within a fault-controlled basin: Late Cretaceous Chaling Basin, South China
Get PDFThe Upper Cretaceous Daijiaping Formation of the Chaling Basin, southeast China, is a mixed aeolian–fluvial succession accumulated in an erg-margin setting. The roles of climate and tectonics in governing the temporal and spatial arrangement of aeolian and fluvial strata are investigated using lithofacies and architectural-element analyses of outcrops in the eastern part of the basin. Architectural elements of aeolian origin record the preserved expression of dunes, sandsheets, damp and wet interdunes, and sand pods. Architectural elements of alluvial origin record channelized bedload streams and cobble-sand sheetflow units. Distinctive deflation lags and desert pavements are also recognized. The alternating nature of deposition via aeolian and aqueous processes is marked by a series of sand-drift surfaces that form a record of repeated shifts from aeolian to water-lain depositional conditions. Ephemeral water influx to the desert-margin system likely occurred in response to exceptional rainfall caused by monsoonal water discharge and meltwaters from glaciated mountain ranges that bordered the basin. The vertical arrangements of alternating facies associations define stacked wetting-upward cycles, each 0.4–14.2 m thick. Each cycle commences with simple or compound crescentic dune deposits, else with aeolian sandsheet deposits. These are overlain by bedload stream or conglomerate sheetflow deposits. The vertical stacking of these different architectural elements records the contraction and expansion of erg-margin systems in response to climate-controlled variations in the groundwater level, sand availability for aeolian transport, and fluvial and aeolian sediment transport capacity. The stratigraphic evolution was controlled by exceptional rainfall events at the basin margin, consequent floods into the dune-field margin and associated fluctuations in the water-table level. Orogenic uplift, a subtropical high-pressure system, and a variable groundwater level controlled by a monsoon climate and tectonic subsidence resulted in the development of extensive aeolian desert depositional systems in the South China hinterland during the Late Cretaceous
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