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MSK1 downstream signaling contributes to inflammatory pain in the superficial spinal dorsal horn
No full textThe nuclear kinases mitogen- and stress-activated kinase 1 and 2 (MSK1 and MSK2), through regulating transcriptional processes, are pivotal for various adaptive responses, including inflammation, learning and addiction. Transcriptional alterations in neurons and glia cells within the pain signal-processing (nociceptive) pathway, including the superficial spinal dorsal horn (SSDH), are critical for the development and persistence of inflammatory pain that results from tissue injuries and subsequent inflammatory reactions. While previous reports have indicated that MSK1 contributes to transcriptional changes in inflamed tissues, the impact of MSK1 on nociceptive processing in the SSDH are poorly understood at present. Here, we report MSK1 immunoreactivity (IR) in a group of excitatory and inhibitory neurons as well as in microglia and oligodendrocytes in the SSDH. Injecting Complete Freund’s Adjuvant into the mouse hind paw produced robust non-evoked pain-related behavior, which was significantly attenuated by global depletion of MSK1. In wild-type mice, the inflammatory pain was accompanied by transient MSK1-dependent phosphorylation of the MSK1 downstream effector histone 3 at serine 10 at one hour but not two days after the injection; still, the number of nuclei exhibiting activated MSK1 expression remained highly restricted even at 1 h post-injection. Our data indicate that MSK1 contributes to inflammatory pain via epigenetic and transcriptional alterations; however, once initiated, MSK1’s downstream effects do not require further drive from the persistent activity of the MSK1 signaling pathway in the SSDH
RAD51AP1 is a versatile RAD51 modulator
No full textRAD51AP1 is an emergent key factor in homologous recombination (HR), the major pathway for accurate repair of DNA double-strand breaks, and in alternative lengthening of telomeres (ALT). Depletion of RAD51AP1 diminishes HR and overexpression is common in cancer, where it is associated with malignancy. Here, we show that RAD51AP1 has a hitherto unknown role in modulating the RAD51 recombinase, the central player in HR. Through a combination of biochemistry and structural biology, we reveal that RAD51AP1 possesses at least three RAD51-binding sites that facilitate its binding across two adjacent RAD51 molecules. We uncover a previously unidentified RAD51-binding mode that stabilizes the RAD51 N-terminal domain and protomer interface in the filaments. We uncover a previously undescribed role for RAD51AP1 in stabilizing RAD51-ssDNA filaments and promoting strand exchange. Our structural data provide the molecular basis for how RAD51AP1 binding induces conformational changes that promote RAD51 DNA association and oligomerization, therefore promoting filament nucleation, stabilization, and strand exchange. Further, we resolved structures of RAD51-ssDNA filaments in the presence of Mg2+-ATP and upon hydrolysis to Mg2+-ADP, revealing that RAD51 filaments expand upon ATP hydrolysis and explaining how ADP reduces RAD51–DNA binding. Our findings reveal RAD51AP1 as a versatile RAD51 modulator and RAD51 filament remodeler and shed previously unidentified insights into the modulation of HR, which is critical for the maintenance of genome stability
Defluoroalkylation of trifluoromethane with organolithium reagents: mechanism and synthesis of fluoroalkenes
No full textTrifluoromethane (HCF3, HFC-23) is a byproduct of fluoropolymer production that has limited applications. It is often stored or destroyed at the point of production, but if released into the environment is a potent greenhouse gas with a global warming potential of 14 600 times that of CO2. State-of-the-art chemical technologies for upgrading HCF3 typically occur with conservation of the CF3 group. These approaches will come under increased scrutiny as concern over the environmental impact of perfluoroalkyl substances (PFAS) continues to grow. A more sustainable approach involves synthetic transformations that repurpose the atomic content of HCF3 while also destroying the CF3 group. In this paper, we report a rare example of the transformation of HCF3 into a fluoroalkene functional group through defluoroalkylation. We rationalise product formation through DFT calculations, scale-up the synthesis through continuous flow methods, and show that a fluoroalkene reagent derived from HCF3 is a competent nucleophile for the fluoroethenylation of a range of aldehydes
Global variation in the ratio of sapwood to leaf area explained by optimality principles
No full text• The sapwood area supporting a given leaf area (Huber value, vH) reflects the coupling between carbon uptake and water transport and loss at a whole-plant level. Geographic variation in vH presumably reflect plant strategic adaptations but the lack of a general explanation for such variation hinders its representation in vegetation models and assessment of how its impact on the global carbon and water cycles.
• Here we develop a simple hydraulic trait model to predict optimal vH by matching stem water supply and leaf water loss, and test its performance against two extensive plant hydraulic datasets.
• We show that our eco-evolutionary optimality-based model explains nearly 60% of global vH variation in response to light, vapour pressure deficit, temperature and sapwood conductivity. Enhanced hydraulic efficiency with warmer temperatures reduces the sapwood area required to support a given leaf area, whereas high irradiance (supporting increased photosynthetic capacity) and drier air increase it.
• This study thus provides a route to modelling variation in functional traits through the coordination of carbon uptake and water transport processes
Paediatric major lower limb absence: demographics of children accessing three prosthetic rehabilitation centres in Cambodia
No full textIntroduction: Demographic and clinical characteristic data for children with major lower limb absence provides insight for rehabilitation professionals and policy makers. This paper describes demographics for children accessing three prosthetic rehabilitation centres in Cambodia. It is hypothesised that associations exist between the demographic data and reason for limb absence as well as time to first prosthetic access.
Method: A retrospective analysis of 71 physical casefiles was conducted for children aged 5-17years in three centres affiliated with Exceed Worldwide and the Department of Prosthetics and Orthotics Cambodia between 2005-2023. Demographic data were extracted for children with major lower limb absence proximal to the ankle joint. Descriptive and inferential statistics were applied with the significance level set at (p<0.05).
Results: 67.6% of children were male and 55.3% of prosthesis provided were transtibial. The most common cause was trauma (59.2%) primarily due to road traffic accidents (71.4%). There was a significant association between reason for limb absence with sex (p=0.004) and
time to prosthetic access (p=0.011). Reason for limb absence (p=0.016) and age of acquired limb absence (p=0.003) were significantly associated with the type of prosthetic supplied.
Conclusion: Traumatic amputation was the most common, with more males and transfemoral children presenting with trauma than expected, necessitating further research into policies to reduce traumatic amputation and it’s subsequent proximal amputations. Time to first access was greater for congenital deficiencies necessitating future work to support early prosthetic use. The dataset provides clarity on a unique cohort requiring ongoing prosthetic care
Biochemical surface patterning in microfluidic devices
No full textThe capacity to pattern biomolecules within microfluidic devices expands the scope of microfluidic technologies. In such patterned systems, surface-bound components remain localized, while the microfluidic network supplies reagents and removes waste products. This approach has enabled continuous protein expression from patterned DNA, chemical synthesis from immobilized enzymes, and cell capture assays. Here, we review methods to pattern surfaces within microfluidic devices. Patterns may be printed before or after the device is assembled; pre-bonding methods are compatible with well-established open-surface patterning protocols but present challenges for device bonding and alignment. Conversely, post-bonding methods are compatible with standard bonding procedures but rely on less established, sequential patterning protocols. Future progress will require consistent reporting of pattern signal and noise relative to controls
Psychological and contextual drivers of indoor air quality behaviours in a deprived urban community: evidence from participatory research
No full textIndoor air pollution poses significant health risks, disproportionately affecting deprived communities that often face higher levels of exposure. This study, conducted as part of the WellHome project, employed a longitudinal design and a participatory research approach, directly involving 110 residents of a deprived urban area in West London in indoor air quality research. It tested an adapted Health Belief Model (HBM), tailored to indoor air quality behaviours, to examine how perceived vulnerability, perceived severity, self-efficacy, perceptions of indoor and outdoor air quality, and contextual cues to action relate to behavioural changes aimed at improving indoor air quality. It also assessed whether these factors predicted behaviour change over time, and explored patterns across various household behaviours, such as cooking, cleaning, heating, smoking, personal care, home fragrance use, window opening, and air purifier use. Results show that self-efficacy, perceived severity, perceptions of indoor and outdoor air quality, and cues to action were significantly associated with behaviour change, while perceived vulnerability was not. Notably, the influence of self-efficacy on behaviour increased over time, underscoring its role in sustaining long-term change. Visible cues, such as mould and damp, emerged as strong contextual triggers for action. Among the behaviours assessed, changes were most frequently reported in window opening, cooking, and cleaning, although a clear increase in change over time was only observed for cooking and heating. These findings suggest that a participatory approach can be effective in promoting healthier indoor environments in vulnerable communities
Correction to: Inverse design of periodic microstructures with targeted nonlinear mechanical behaviour
No full textIn the original version of this article has error in the Eq. (21). The corrected equation is shown below. (Formula presented.) The original article has been corrected
LED-pumped room-temperature solid-state maser
No full textRoom-temperature MASERs (Microwave Amplification by Stimulated Emission of Radiation) amplify electromagnetic waves at microwave frequencies with minimal noise. We demonstrate a cost-effective LED-pumped maser using pentacene-doped para-terphenyl as the gain medium. Here, we show that LED light, which is brightness-enhanced and guided via a cerium-doped yttrium aluminium garnet luminescent concentrator, achieves persistent maser emission at 1.45 GHz with a duration of 200 µs and a microwave output power of 0.014 mW, surpassing previous non-laser pumped systems. Operating at low voltage, the LED-pumped maser ensures safety, reduced costs, and simple integration. Potential applications include sensitive magnetic resonance imaging, portable atomic clocks, quantum technologies, and enhanced deep-space radio astronomy
Social media use and child cigarette smoking and e-cigarette use: a cohort study 2015-2023
No full textIntroduction
There are growing concerns that advertising and promotion on social media are driving youth use of tobacco and e-cigarettes. The UK provides an instructive example as it has high levels of e-cigarette use, high levels of social media use and a restrictive tobacco control environment. Existing evidence in the UK however, has not focused on children, has not been updated to reflect changes in patterns of social media use and in the use of these products. The aim of this study is to assess the associations of social media use with smoking and vaping.
Methods
Using data from the United Kingdom Household Longitudinal Study on 10–17-year-olds between 2015-2023, Generalised Estimating Equation (GEE) models estimated relationships between time spent on social media and likelihood of smoking tobacco and using e-cigarettes. Models were controlled for possible confounders including socio-demographics and whether children lived in a home with e-cigarette use or tobacco smoking.
Results
We included data from 9,359 participants with 25,704 observations. Current cigarette smoking was reported by 4.9% of the sample and current e-cigarette use by 3.1% of the sample. Our adjusted models found strong relationships between time spent on social media and both smoking and vaping (p value for trend <0.001). For example, use of social media for ≥7 hours/day was linked to greater odds of tobacco (Adjusted Odds Ratio (AOR) 5.13, 95% Confidence Interval (CI) 3.32-7.95) and e-cigarette use (AOR 4.26, CI 2.25-8.08).
Conclusions
This study finds associations between time spent on social media and both smoking and vaping among children. Enforcing regulations on content and restricting the duration of social media use may be warranted to protect children’s health